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Membrane Organization and Dynamics pp 195–217Cite as

Spatiotemporal Dynamics of Nicotinic Acetylcholine Receptors and Lipid Platforms

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Part of the book series: Springer Series in Biophysics ((BIOPHYSICS,volume 20))

Abstract

The relationships between neurotransmitter receptors and their membrane environment are complex, mutual (bidirectional) and physiologically important. Some of these relationships are established with subsets of the membrane lipid population, in the form of lipid platforms, lateral heterogeneities of the bilayer lipid having a dynamic chemical composition distinct from that of the bulk membrane. In addition to the equilibrium between the biosynthetic production, exocytic delivery and recycling of receptors on the one hand, and the endocytic internalization on the other, lateral diffusion, clustering and anchorage of receptors at the lipid platforms play key roles in determining the amount of active receptors at the synapse. Mobile receptors traffic between reservoir non-synaptic membranes and the synapse predominantly by thermally driven Brownian motion, and become immobilized at the perisynaptic region or the synapse proper by various mechanisms. These comprise: (a) clustering mediated by homotropic inter-molecular receptor-receptor associations; (b) heterotropic associations with non-receptor scaffolding proteins or the subjacent cytoskeletal meshwork, leading to diffusional “trapping”, and (c) protein-lipid interactions, particularly with the neutral lipid cholesterol. Preceded by a brief introduction on the currently used methods to study protein lateral mobility in membranes, this review assesses the contribution of some of these mechanisms to the supramolecular organization and dynamics of the paradigm neurotransmitter receptor of muscle and neuronal cells—the nicotinic acetylcholine receptor (nAChR). The translational mobility of nAChRs at these two cell surfaces differs in terms of diffusion coefficients and residence intervals at the synapse, which cover an ample range of time regimes. Neuronal α7 nAChRs exhibit diffusion coefficients similar to those of other neurotransmitter receptors and spend part of their lifetime confined to the perisynaptic region of glutamatergic (excitatory) and GABAergic (inhibitory) synapses; they may also be involved in the regulation of the dynamic equilibrium between excitation and inhibition in brain.

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Abbreviations

αBTX:

α-Bungarotoxin

FCS:

Fluorescence correlation spectroscopy

FRAP:

Fluorescence recovery after photobleaching

MSD:

Mean-square displacement

nAChR:

Nicotinic acetylcholine receptor

SPT:

Single particle tracking

TIRF:

Total internal reflection fluorescence

References

  1. Chen Y, Lagerholm BC, Yang B, Jacobson K. Methods to measure the lateral diffusion of membrane lipids and proteins. Methods. 2006;39(2):147–53.

    Article  PubMed  CAS  Google Scholar 

  2. Jacobson K, Mouritsen OG, Anderson RG. Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol. 2007;9(1):7–14.

    Article  PubMed  CAS  Google Scholar 

  3. Kusumi A, Nakada C, Ritchie K, Murase K, Suzuki K, Murakoshi H, Kasai RS, Kondo J, Fujiwara T. Paradigm shift of the plasma membrane concept from the two-dimensional continuum fluid to the partitioned fluid: high-speed single-molecule tracking of membrane molecules. Annu Rev Biophys Biomol Struct. 2005;34:351–78.

    Article  PubMed  CAS  Google Scholar 

  4. Kusumi A, Sako Y, Yamamoto M. Confined lateral diffusion of membrane receptors as studied by single particle tracking (nanovid microscopy). Effects of calcium-induced differentiation in cultured epithelial cells. Biophys J. 1993;65(5):2021–40.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  5. Suzuki K, Ritchie K, Kajikawa E, Fujiwara T, Kusumi A. Rapid hop diffusion of a G-protein-coupled receptor in the plasma membrane as revealed by single-molecule techniques. Biophys J. 2005;88(5):3659–80.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Rao M, Mayor S. Rafts: scale-dependent, active lipid organization at the cell surface. Traffic. 2004;5:231–40.

    Article  PubMed  CAS  Google Scholar 

  7. Rao M, Mayor S. Active organization of membrane constituents in living cells. Curr Opin Cell Biol. 2014;29:126–32.

    Article  PubMed  CAS  Google Scholar 

  8. Varma R, Mayor S. GPI-anchored proteins are organized in submicron domains at the cell surface. Nature. 1998;394:798–801.

    Article  PubMed  CAS  Google Scholar 

  9. Borroni MV, Vallés AS, Barrantes FJ. The lipid habitats of neurotransmitter receptors in brain. Biochim Biophys Acta Biomembr. 2016;1858(11):2662–70.

    Article  CAS  Google Scholar 

  10. Barrantes FJ. Phylogenetic conservation of protein-lipid motifs in pentameric ligand-gated ion channels. Biochim Biophys Acta Biomembr. 2015;1848(9):1796–805.

    Article  CAS  Google Scholar 

  11. Barrantes FJ, Fantini J. From hopanoids to cholesterol: molecular clocks of pentameric ligand-gated ion channels. Prog Lipid Res. 2016;63:1–13.

    Article  PubMed  CAS  Google Scholar 

  12. Kang M, Day CA, Drake K, Kenworthy AK, DiBenedetto E. A generalization of theory for two-dimensional fluorescence recovery after photobleaching applicable to confocal laser scanning microscopes. Biophys J. 2009;97(5):1501–11.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Petersen NO, Elson EL. Measurements of diffusion and chemical kinetics by fluorescence photobleaching recovery and fluorescence correlation spectroscopy. Methods Enzymol. 1986;130:454–84.

    Article  PubMed  CAS  Google Scholar 

  14. Andrade DM, Clausen MP, Keller J, Mueller V, Wu C, Bear JE, Hell SW, Lagerholm BC, Eggeling C. Cortical actin networks induce spatio-temporal confinement of phospholipids in the plasma membrane – a minimally invasive investigation by STED-FCS. Sci Rep. 2015;5. https://doi.org/10.1038/srep11454.

  15. Eggeling C, Ringemann C, Medda R, Schwarzmann G, Sandhoff K, Polyakova S, Belov VN, Hein B, von Middendorff C, Schonle A, Hell SW. Direct observation of the nanoscale dynamics of membrane lipids in a living cell. Nature. 2009;457(7233):1159–62.

    Article  PubMed  CAS  Google Scholar 

  16. Elson EL. Quick tour of fluorescence correlation spectroscopy from its inception. J Biomed Opt. 2004;9(5):857–64.

    Article  PubMed  CAS  Google Scholar 

  17. Elson EL, Qian H. Interpretation of fluorescence correlation spectroscopy and photobleaching recovery in terms of molecular interactions. Methods Cell Biol. 1989;30:307–32.

    Article  PubMed  CAS  Google Scholar 

  18. Schwille P. Fluorescence correlation spectroscopy and its potential for intracellular applications. Cell Biochem Biophys. 2001;34(3):383–408.

    Article  PubMed  CAS  Google Scholar 

  19. Schwille P, Haupts U, Maiti S, Webb WW. Molecular dynamics in living cells observed by fluorescence correlation spectroscopy with one- and two-photon excitation. Biophys J. 1999;77(4):2251–65.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Sengupta P, Balaji J, Maiti S. Measuring diffusion in cell membranes by fluorescence correlation spectroscopy. Methods. 2002;27(4):374–87.

    Article  PubMed  CAS  Google Scholar 

  21. Day CA, Kenworthy AK. Tracking microdomain dynamics in cell membranes. Biochim Biophys Acta. 2009;1788(1):245–53.

    Article  PubMed  CAS  Google Scholar 

  22. Qian H, Sheetz MP, Elson EL. Single particle tracking. Analysis of diffusion and flow in two-dimensional systems. Biophys J. 1991;60(4):910–21.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Saxton MJ. Single-particle tracking: effects of corrals. Biophys J. 1995;69(2):389–98.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Saxton MJ, Jacobson KA. Single-particle tracking: applications to membrane dynamics. Annu Rev Biophys Biomol Struct. 1997;26:373–99.

    Article  PubMed  CAS  Google Scholar 

  25. Simson R, Sheets ED, Jacobson K. Detection of temporary lateral confinement of membrane proteins using single-particle tracking analysis. Biophys J. 1995;69(3):989–93.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Simson R, Yang B, Moore SE, Doherty P, Wash FS, Jacobson KA. Structural mosaicism on the submicron sacale in the plasma membrane. Biophys J. 1998;74(1):297–308.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Wu H-M, Lin Y-H, Yen T-C, Hsieh C-L. Nanoscopic substructures of raft-mimetic liquid-ordered membrane domains revealed by high-speed single-particle tracking. Sci Rep. 2016;6:20542.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Kim SA, Schwille P. Intracellular applications of fluorescence correlation spectroscopy: prospects for neuroscience. Curr Opin Neurobiol. 2003;13:583–90.

    Article  PubMed  CAS  Google Scholar 

  29. Eggeling C, Willig KI, Barrantes FJ. STED microscopy of living cells—new frontiers in membrane and neurobiology. J Neurochem. 2013;126(2):203–12.

    Article  PubMed  CAS  Google Scholar 

  30. Digman M, Gratton E. Imaging barriers to diffusion by pair correlation functions. Biophys J. 2009;97:665–73.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. Sahl S, Leutenegger M, Hell S, Eggeling C. High-resolution tracking of single-molecule diffusion in membranes by confocalized and spatially differentiated fluorescence photon stream recording. ChemPhysChem. 2014;15(4):771–83.

    Article  PubMed  CAS  Google Scholar 

  32. Dietrich C, Yang B, Fujiwara T, Kusumi A, Jacobson K. Relationship of lipid rafts to transient confinement zones detected by single particle tracking. Biophys J. 2002;82(1 Pt 1):274–84.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  33. Kapitza HG, McGregor G, Jacobson KA. Direct measurement of lateral transport in membranes by using time-resolved spatial photometry. Proc Natl Acad Sci U S A. 1985;82(12):4122–6.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  34. Ladha S, Mackie AR, Clark DC. Cheek cell membrane fluidity measured by fluorescence recovery after photobleaching and steady-state fluorescence anisotropy. J Membr Biol. 1994;142(2):223–8.

    Article  PubMed  CAS  Google Scholar 

  35. Niv H, Gutman O, Kloog Y, Henis YI. Activated K-Ras and H-Ras display different interactions with saturable nonraft sites at the surface of live cells. J Cell Biol. 2002;157(5):865–72.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  36. Pucadyil TJ, Mukherjee S, Chattopadhyay A. Organization and dynamics of NBD-labeled lipids in membranes analyzed by fluorescence recovery after photobleaching. J Phys Chem B. 2007;111(8):1975–83.

    Article  PubMed  CAS  Google Scholar 

  37. Masson JB, Dionne P, Salvatico C, Renner M, Specht CG, Triller A, Dahan M. Mapping the energy and diffusion landscapes of membrane proteins at the cell surface using high-density single-molecule imaging and Bayesian inference: application to the multiscale dynapics of glycine receptors in the neuronal membrane. Biophys J. 2014;106:74–83.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Monnier N, Guo S-M, Mori M, He J, Lenart P, Bathe M. Bayesian approach to MSD-based analysis of particle motion in live cells. Biophys J. 2012;103:616–26.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  39. Türkcan S, Alexandrou A, Masson JB. A Bayesian inference scheme to extract diffusivity and potential fields from confined single-molecule trajectories. Biophys J. 2012;102:2288–98.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  40. Türkcan S, Masson JB. Bayesian decision free for the classification of the model of motion in single-molecule trajectories. PLoS One. 2013;8:e82799.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  41. Manzo C, van Zanten TS, Saha S, Torreno-Pina JA, Mayor S, G.-P. M.F. PSF decomposition of nanoscopy images via Bayesian analysis unravels distinct molecular organization of the cell membrane. Sci Rep. 2014;4:4354.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  42. Chenouard N, Smal I, de Chaumont F, Maška M, Sbalzarini IF, Gong Y, Cardinale J, Carthel C, Coraluppi S, Winter M, Cohen AR, Godinez WJ, Rohr K, Kalaidzidis Y, Liang L, Duncan J, Shen H, Xu Y, Magnusson KE, Jaldén J, Blau HM, Paul-Gilloteaux P, Roudot P, Kervrann C, Waharte F, Tinevez JY, Shorte SL, Willemse J, Celler K, van Wezel GP, Dan HW, Tsai YS, Ortiz de Solórzano C, Olivo-Marin JC, Meijering E. Objective comparison of particle tracking methods. Nat Methods. 2014;11:281–9.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  43. Cecchini M, Changeux JP. The nicotinic acetylcholine receptor and its prokaryotic homologues: structure, conformational transitions & allosteric modulation. Neuropharmacology. 2015;96(Pt B):137–49.

    Article  PubMed  CAS  Google Scholar 

  44. Nys M, Kesters D, Ulens C. Structural insights into Cys-loop receptor function and ligand recognition. Biochem Pharmacol. 2013;86:1042–53.

    Article  PubMed  CAS  Google Scholar 

  45. Barrantes FJ. Modulation of nicotinic acetylcholine receptor function through the outer and middle rings of transmembrane domains. Curr Opin Drug Discov Devel. 2003;6(5):620–32.

    PubMed  CAS  Google Scholar 

  46. Karlin A. Emerging structure of the nicotinic acetylcholine receptors. Nat Rev Neurosci. 2002;3:102–14.

    Article  PubMed  CAS  Google Scholar 

  47. Barrantes FJ. Endogenous chemical receptors: some physical aspects. Annu Rev Biophys Bioeng. 1979;8:287–321.

    Article  PubMed  CAS  Google Scholar 

  48. Sanes JR, Lichtman JW. Induction, assembly, maturation and maintenance of a postsynaptic apparatus. Nat Rev Neurosci. 2001;2(11):791–805.

    Article  PubMed  CAS  Google Scholar 

  49. Salpeter MM, Loring RH. Nicotinic acetylcholine receptors in vertebrate muscle: properties, distribution and neural control. Prog Neurobiol. 1985;25(4):297–325.

    Article  PubMed  CAS  Google Scholar 

  50. Pierron M, Pinan-Lucarre B, Bessereau JL. Preventing illegitimate extrasynaptic acetylcholine receptor clustering requires the RSU-1 protein. J Neurosci. 2016;36(24):6525–37.

    Article  PubMed  CAS  Google Scholar 

  51. Burden SJ, Yumoto N, Zhang W. The role of MuSK in synapse formation and neuromuscular disease. Cold Spring Harb Perspect Biol. 2013;5(5):a009167.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  52. Picciotto MR, Higley MJ, Mineur YS. Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron. 2012;76(1):116–29.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  53. Descarries L, Gisiger V, Steriade M. Diffuse transmission by acetylcholine in the CNS. Prog Neurobiol. 1997;53(5):603–25.

    Article  PubMed  CAS  Google Scholar 

  54. Descarries L, Parent M. Chapter 14 – Asynaptic and synaptic innervation by acetylcholine neurons of the central nervous system. In: Pickel V, Segal M, editors. The synapse. Boston: Academic Press; 2014. p. 447–66.

    Chapter  Google Scholar 

  55. Choquet D, Triller A. The role of receptor diffusion in the organization of the postsynaptic membrane. Nat Rev Neurosci. 2003;4(4):251–65.

    Article  PubMed  CAS  Google Scholar 

  56. Choquet D, Triller A. The dynamic synapse. Neuron. 2013;80:691–703.

    Article  PubMed  CAS  Google Scholar 

  57. Holcman D, Triller A. Modeling synaptic dynamics driven by receptor lateral diffusion. Biophys J. 2006;91(7):2405–15.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  58. Triller A, Choquet D. New concepts in synaptic biology derived from single-molecule imaging. Neuron. 2008;59(3):359–74.

    Article  PubMed  CAS  Google Scholar 

  59. Bear MF, Malenka RC. Synaptic plasticity: LTP and LTD. Curr Opin Neurobiol. 1994;4(3):389–99.

    Article  PubMed  CAS  Google Scholar 

  60. Kroker KS, Rast G, Rosenbrock H. Differential effects of subtype-specific nicotinic acetylcholine receptor agonists on early and late hippocampal LTP. Eur J Pharmacol. 2011;671(1–3):26–32.

    Article  PubMed  CAS  Google Scholar 

  61. Stevens C. A millon dollar question: does LTP = memory? Neuron. 1998;20:1–2.

    Article  PubMed  CAS  Google Scholar 

  62. Chen L, Yamada K, Nabeshima T, Sokabe M. α7 nicotinic acetylcholine receptor as a target to rescue deficit in hippocampal LTP induction in β-amyloid infused rats. Neuropharmacology. 2006;50(2):254–68.

    Article  PubMed  CAS  Google Scholar 

  63. Ma L, Turner D, Zhang J, Wang Q, Wang M, Shen J, Zhang S, Wu J. Deficits of synaptic functions in hippocampal slices prepared from aged mice null α7 nicotinic acetylcholine receptors. Neurosci Lett. 2014;570:97–101.

    Article  PubMed  CAS  Google Scholar 

  64. Ondrejcak T, Wang Q, Kew JNC, Virley DJ, Upton N, Anwyl R, Rowan MJ. Activation of α7 nicotinic acetylcholine receptors persistently enhances hippocampal synaptic transmission and prevents Aß-mediated inhibition of LTP in the rat hippocampus. Eur J Pharmacol. 2012;677(1–3):63–70.

    Article  PubMed  CAS  Google Scholar 

  65. Broide RS, Leslie FM. The alpha7 nicotinic acetylcholine receptor in neuronal plasticity. Mol Neurobiol. 1999;20(1):1–16.

    Article  PubMed  CAS  Google Scholar 

  66. Axelrod D, Koppel DE, Schlessinger J, Elson E, Webb WW. Mobility measurement by analysis of fluorescence photobleaching recovery kinetics. Biophys J. 1976;16(9):1055–69.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  67. Heuser JE, Salpeter SR. Organization of acetylcholine receptors in quick-frozen, deep-etched, and rotary-replicated Torpedo postsynaptic membrane. J Cell Biol. 1979;82:150–73.

    Article  PubMed  CAS  Google Scholar 

  68. Roccamo AM, Pediconi MF, Aztiria E, Zanello L, Wolstenholme A, Barrantes FJ. Cells defective in sphingolipids biosynthesis express low amounts of muscle nicotinic acetylcholine receptor. Eur J Neurosci. 1999;11(5):1615–23.

    Article  PubMed  CAS  Google Scholar 

  69. Kumari S, Borroni V, Chaudhry A, Chanda B, Massol R, Mayor S, Barrantes FJ. Nicotinic acetylcholine receptor is internalized via a Rac-dependent, dynamin-independent endocytic pathway. J Cell Biol. 2008;181(7):1179–93.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  70. Nehls S, Snapp EL, Cole NB, Zaal KJ, Kenworthy AK, Roberts TH, Ellenberg J, Presley JF, Siggia E, Lippincott-Schwartz J. Dynamics and retention of misfolded proteins in native ER membranes. Nat Cell Biol. 2000;2(5):288–95.

    Article  PubMed  CAS  Google Scholar 

  71. Zaal KJ, Smith CL, Polishchuk RS, Altan N, Cole NB, Ellenberg J, Hirschberg K, Presley JF, Roberts TH, Siggia E, Phair RD, Lippincott-Schwartz J. Golgi membranes are absorbed into and reemerge from the ER during mitosis. Cell. 1999;99(6):589–601.

    Article  PubMed  CAS  Google Scholar 

  72. Edidin M. Fluorescence photobleaching and recovery, FPR, in the analysis of membrane structure and dynamics. In: Damjanocich S, Edidin M, Szollosi J, editors. Mobility and proximity in biological membranes. Boca Raton, FL: CRC Press; 1994. p. 109–35.

    Google Scholar 

  73. Guo L, Har JY, Sankaran J, Hong Y, Kannan B, Wohland T. Molecular diffusion measurement in lipid bilayers over wide concentration ranges: a comparative study. ChemPhysChem. 2008;9(5):721–8.

    Article  PubMed  CAS  Google Scholar 

  74. Kenworthy AK, Nichols BJ, Remmert CL, Hendrix GM, Kumar M, Zimmerberg J, Lippincott-Schwartz J. Dynamics of putative raft-associated proteins at the cell surface. J Cell Biol. 2004;165(5):735–46.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  75. Baier CJ, Gallegos CE, Levi V, Barrantes FJ. Cholesterol modulation of nicotinic acetylcholine receptor surface mobility. Eur Biophys J. 2010;39(2):213–27.

    Article  PubMed  CAS  Google Scholar 

  76. Stya M, Axelrod D. Mobility and detergent extractability of acetylcholine receptors on cultured rat myotubes: a correlation. J Cell Biol. 1983;97:48–51.

    Article  PubMed  CAS  Google Scholar 

  77. Stya M, Axelrod D. Mobility of extrajunctional acetylcholine receptors on denervated adult muscle fibers. J Neurosci. 1984;4:70–4.

    PubMed  CAS  Google Scholar 

  78. Borroni V, Baier CJ, Lang T, Bonini I, White MM, Garbus I, Barrantes FJ. Cholesterol depletion activates rapid internalization of submicron-sized acetylcholine receptor domains at the cell membrane. Mol Membr Biol. 2007;24(1):1–15.

    Article  PubMed  CAS  Google Scholar 

  79. Kellner RR, Baier CJ, Willig KI, Hell SW, Barrantes FJ. Nanoscale organization of nicotinic acetylcholine receptors revealed by stimulated emission depletion microscopy. Neuroscience. 2007;144(1):135–43.

    Article  PubMed  CAS  Google Scholar 

  80. Almarza G, Sanchez F, Barrantes FJ. Transient cholesterol effects on nicotinic acetylcholine receptor cell-surface mobility. PLoS One. 2014;9(6):e100346.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Simonson PD, DeBerg HA, Ge P, Alexander JK, Jeyifous O, Green WN, Selvin PR. Counting bungarotoxin binding sites of nicotinic acetylcholine receptors in mammalian cells with high signal/noise ratios. Biophys J. 2010;99(10):L81–3.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  82. Barrantes FJ, Neugebauer DC, Zingsheim HP. Peptide extraction by alkaline treatment is accompanied by rearrangement of the membrane-bound acetylcholine receptor from Torpedo marmorata. FEBS Lett. 1980;112(1):73–8.

    Article  PubMed  CAS  Google Scholar 

  83. Burden SJ, Depalma RL, Gottesman GS. Crosslinking of proteins in acetylcholine receptor-rich membranes: association between the β-subunit and the 43 kd subsynaptic protein. Cell. 1983;35:687–92.

    Article  PubMed  CAS  Google Scholar 

  84. Ramarao MK, Cohen JB. Mechanism of nicotinic acetylcholine receptor cluster formation by rapsyn. Proc Natl Acad Sci U S A. 1998;95:4007–12.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  85. Piguet J, Schreiter C, Segura J, Voguel H, Hovius R. Acetylcholine receptor organization in membrane domains in muscle cells: evidence for rapsyn-independent and rapsyn-dependent mechanisms. Int J Biol Chem. 2011:363–9.

    Google Scholar 

  86. O’Connell KM, Tamkun MM. Targeting of voltage-gated potassium channel isoforms to distinct cell surface microdomains. J Cell Sci. 2005;118(Pt 10):2155–66.

    Article  PubMed  CAS  Google Scholar 

  87. Nishimura SY, Vrljic M, Klein LO, McConnell HM, Moerner WE. Cholesterol depletion induces solid-like regions in the plasma membrane. Biophys J. 2006;90(3):927–38.

    Article  PubMed  CAS  Google Scholar 

  88. Vrljic M, Nishimura SY, Moerner WE, McConnell HM. Cholesterol depletion suppresses the translational diffusion of class II major histocompatibility complex proteins in the plasma membrane. Biophys J. 2005;88(1):334–47.

    Article  PubMed  CAS  Google Scholar 

  89. Sun M, Northup N, Marga F, Huber T, Byfield FJ, Levitan I, et al. The effect of cellular cholesterol on membrane-cytoskeleton adhesion. J. Cell Sci. 2007;120(Pt 13):2223–31. doi:10.1242/jcs.001370.

    Article  PubMed  CAS  Google Scholar 

  90. Orr G, Hu D, Ozcelik S, Opresko LK, Wiley HS, Colson SD. Cholesterol dictates the freedom of EGF receptors and HER2 in the plane of the membrane. Biophys J. 2005;89(2):1362–73.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  91. Oliferenko S, Paiha K, Harder T, Gerke V, Schwarzler C, Schwarz H, Beug H, Gunthert U, Huber LA. Analysis of CD44-containing lipid rafts: recruitment of annexin II and stabilization by the actin cytoskeleton. J Cell Biol. 1999;146(4):843–54.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  92. Shvartsman DE, Gutman O, Tietz A, Henis YI. Cyclodextrins but not compactin inhibit the lateral diffusion of membrane proteins independent of cholesterol. Traffic. 2006;7(7):917–26.

    Article  PubMed  CAS  Google Scholar 

  93. Bruses J, Chauvet N, Rutishauser U. Membrane lipid rafts are necessary for the maintenance of the (alpha)7 nicotinic acetylcholine receptor in somatic spines of ciliary neurons. J Neurosci. 2001;21(2):504–12.

    PubMed  CAS  Google Scholar 

  94. Gomez-Varela D, Kohl T, Schmidt M, Rubio ME, Kawabe H, Nehring RB, Schafer S, Stuhmer W, Pardo LA. Characterization of Eag1 channel lateral mobility in rat hippocampal cultures by single-particle-tracking with quantum dots. PLoS One. 2010;5(1):e8858.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  95. Hotulainen P, Hoogenraad CC. Actin in dendritic spines: connecting dynamics to function. J Cell Biol. 2010;189(4):619–29.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  96. Feder TJ, Brust-Mascher I, Slattery JP, Baird B, Webb WW. Constrained diffusion or immobile fraction on cell surfaces: a new interpretation. Biophys J. 1996;70(6):2767–73.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  97. Bloch RJ, Velez M, Krikorian JG, Axelrod D. Microfilaments and actin-associated proteins at sites of membrane-substrate attachment within acetylcholine receptor clusters. Exp Cell Res. 1989;182:583–96.

    Article  PubMed  CAS  Google Scholar 

  98. Dai Z, Luo X, Xie H, Peng HB. The actin-driven movement and formation of acetylcholine receptor clusters. J Cell Biol. 2000;150(6):1321–34.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  99. Pumplin DW, Strong JC. Acetylcholine receptor clusters of rat myotubes have at least three domains with distinctive cytoskeletal and membranous components. J Cell Biol. 1989;109:739–53.

    Article  PubMed  CAS  Google Scholar 

  100. Honigmann A, Sadeghi S, Keller J, Hell SW, Eggeling C, Vink R. A lipid bound actin meshwork organizes liquid phase separation in model membranes. Elife. 2014;3:e01671.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  101. Lenne P-F, Wawrezinieck L, Conchonaud F, Wurtz O, Boned A, Guo X-J, et al. Dynamic molecular confinement in the plasma membrane by microdomains and the cytoskeleton meshwork. EMBO J. 2006;25:3245–56. doi:10.1038/sj.emboj.7601214.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  102. Maxfield FR. Plasma membrane microdomains. Curr. Opin. Cell Biol. 2002;14:483–7. doi:10.1016/S0955-0674(02)00351-4.

    Article  PubMed  CAS  Google Scholar 

  103. Kwik J, Boyle S, Fooksman D, Margolis L, Sheetz MP, Edidin M. Membrane cholesterol, lateral mobility, and the phosphatidylinositol 4,5-bisphosphate-dependent organization of cell actin. Proc. Natl. Acad. Sci. U.S.A. 2003;100:13964–9. doi:10.1073/pnas.2336102100.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  104. Saka SK, Honigmann A, Eggeling C, Hell SW, Lang T, Rizzoli SO. Multi-protein assemblies underlie the mesoscale organization of the plasma membrane. Nat Commun. 2014;5:1–14.

    Google Scholar 

  105. Kusumi A, Ike H, Nakada C, Murase K, Fujiwara T. Single-molecule tracking of membrane molecules: plasma membrane compartmentalization and dynamic assembly of raft-philic signaling molecules. Semin Immunol. 2005;17(1):3–21.

    Article  PubMed  CAS  Google Scholar 

  106. Triller A, Choquet D. Synaptic structure and diffusion dynamics of synaptic receptors. Biol Cell. 2003;95(7):465–76.

    Article  PubMed  CAS  Google Scholar 

  107. Kusumi A, Suzuki K. Toward understanding the dynamics of membrane-raft-based molecular interactions. Biochim Biophys Acta. 2005;1746(3):234–51.

    Article  PubMed  CAS  Google Scholar 

  108. Ritchie K, Shan XY, Kondo J, Iwasawa K, Fujiwara T, Kusumi A. Detection of non-Brownian diffusion in the cell membrane in single molecule tracking. Biophys J. 2005;88(3):2266–77.

    Article  PubMed  CAS  Google Scholar 

  109. Hoch W. Formation of the neuromuscular junction. Agrin and its unusual receptors. Eur. J. Biochem. 1999;265:1–10. doi:10.1046/j.1432-1327.1999.00765.x.

    Article  PubMed  CAS  Google Scholar 

  110. Wenz JJ, Borroni V, Barrantes FJ. Statistical analysis of high-resolution light microscope images reveals effects of cytoskeleton-disrupting drugs on the membrane organization of the nicotinic acetylcholine receptor. J Membr Biol. 2010;235(3):163–75.

    Article  PubMed  CAS  Google Scholar 

  111. Alexander JK, Govind AP, Drisdel RC, Blanton MP, Vallejo Y, Lam TT, Green WN. Palmitoylation of nicotinic acetylcholine receptors. J Mol Neurosci. 2010;40:12–20.

    Article  PubMed  CAS  Google Scholar 

  112. Drisdel RC, Manzana E, Green WN. The role of palmitoylation in functional expression of nicotinic alpha7 receptors. J Neurosci. 2004;24:10502–10.

    Article  PubMed  CAS  Google Scholar 

  113. Rudell JB, Ferns MJ. Regulation of muscle acetylcholine receptor turnover by β subunit tyrosine phosphorylation. Dev Neurobiol. 2013;73:399–410.

    Article  PubMed  CAS  Google Scholar 

  114. Talwar S, Lynch JW. Phosphorylation mediated structural and functional changes in pentameric ligand-gated ion channels: implications for drug discovery. Int J Biochem Cell Biol. 2014;53:218–23.

    Article  PubMed  CAS  Google Scholar 

  115. Axelrod D. Crosslinkage and visualization of acetylcholine receptors on myotubes with biotinylated alpha-bungarotoxin and fluorescent avidin. Proc Natl Acad Sci U S A. 1980;77(8):4823–7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  116. Sieb JP. Myasthenia gravis: an update for the clinician. Clin Exp Immunol. 2014;175(3):408–18.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  117. Huganir RL, Nicoll RA. AMPARs and synaptic plasticity: the last 25 years. Neuron. 2013;80(3):704–17.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  118. Bashir ZI, Alford S, Davies SN, Randall AD, Collingridge GL. Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus. Nature. 1991;349(6305):156–8.

    Article  PubMed  CAS  Google Scholar 

  119. Cui Z, Wang H, Tan Y, Zaia KA, Zhang S, Tsien JZ. Inducible and reversible NR1 knockout reveals crucial role of the NMDA receptor in preserving remote memories in the brain. Neuron. 2004;41(5):781–93.

    Article  PubMed  CAS  Google Scholar 

  120. Li F, Tsien JZ. Memory and the NMDA receptors. N Engl J Med. 2009;361(3):302–3.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  121. Besshoh S, Bawa D, Teves L, Wallace MC, Gurd JW. Increased phosphorylation and redistribution of NMDA receptors between synaptic lipid rafts and post-synaptic densities following transient global ischemia in the rat brain. J Neurochem. 2005;93(1):186–94.

    Article  PubMed  CAS  Google Scholar 

  122. Frank C, Giammarioli AM, Pepponi R, Fiorentini C, Rufini S. Cholesterol perturbing agents inhibit NMDA-dependent calcium influx in rat hippocampal primary culture. FEBS Lett. 2004;566(1–3):25–9.

    Article  PubMed  CAS  Google Scholar 

  123. Gotti C, Clementi F, Fornari A, Gaimarri A, Guiducci S, Manfredi I, Moretti M, Pedrazzi P, Pucci L, Zoli M. Structural and functional diversity of native brain neuronal nicotinic receptors. Biochem Pharmacol. 2009;78:703–11.

    Article  PubMed  CAS  Google Scholar 

  124. Cuevas J, Berg DK. Mammalian nicotinic receptors with alpha7 subunits that slowly desensitize and rapidly recover from alpha-bungarotoxin blockade. J Neurosci. 1998;18:10335–44.

    PubMed  CAS  Google Scholar 

  125. Fabian-Fine R, Skehel P, Errington ML, Davies HA, Sher E, Stewart MG, Fine A. Ultrastructural distribution of the 7 nicotinic acetylcholine receptor subunit in rat hippocampus. J Neurosci. 2001;21:7993–8003.

    PubMed  CAS  Google Scholar 

  126. Buerli T, Baer K, Ewers H, Sidler C, Fuhrer C, Fritschy JM. Single particle tracking of alpha7 nicotinic AChR in hippocampal neurons reveals regulated confinement at glutamatergic and GABAergic perisynaptic sites. PLoS One. 2010;5(7):e11507.

    Article  CAS  Google Scholar 

  127. Alkondon M, Pereira EF, Barbosa CT, Albuquerque EX. Neuronal nicotinic acetylcholine receptor activation modulates gamma-aminobutyric acid release from CA1 neurons of rat hippocampal slices. Pharmacol Exp Ther. 1997;283:1396–411.

    CAS  Google Scholar 

  128. Alkondon MA, E.X. The nicotinic acetylcholine receptor subtypes and their function in the hippocampus and cerebral cortex. Prog Brain Res. 2004;145:109–20.

    Article  PubMed  CAS  Google Scholar 

  129. Banerjee C, Nyengaard JR, Wevers A, de Vos RA, Jansen Steur EN, Lindstrom J, Pilz K, Nowacki S, Bloch W, Schroder H. Cellular expression of alpha7 nicotinic acetylcholine receptor protein in the temporal cortex in Alzheimer’s and Parkinson’s disease—a stereological approach. Neurobiol Dis. 2000;7:666–72.

    Article  PubMed  CAS  Google Scholar 

  130. Charrier C, Ehrensperger MV, Dahan M, Levy S, Triller A. Cytoskeleton regulation of glycine receptor number at synapses and diffusion in the plasma membrane. J Neurosci. 2006;26:8502–11.

    Article  PubMed  CAS  Google Scholar 

  131. Dahan M, Levi S, Luccardini C, Rostaing P, Riveau B, Triller A. Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science. 2003;302(5644):442–5.

    Article  PubMed  CAS  Google Scholar 

  132. Ehlers MD, Heine M, Groc L, Lee MC, Choquet D. Diffusional trapping of GluR1 AMPA receptors by input-specific synaptic activity. Neuron. 2007;54(3):447–60.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  133. Meier J, Vannier C, Serge A, Triller A, Choquet D. Fast and reversible trapping of surface glycine receptors by gephyrin. Nat Neurosci. 2001;4(3):253–60.

    Article  PubMed  CAS  Google Scholar 

  134. Ehrensperger MV, Hanus C, Vannier C, Triller A, Dahan M. Multiple associations states between glycine receptors and gephyrin identified by SPT analysis. Biophys J. 2007;92:442–5.

    Article  CAS  Google Scholar 

  135. Allison DW, Gelfand VI, Spector I, Craig AM. Role of actin in anchoring postsynaptic receptors in cultured hippocampal neurons: differential attachment of NMDA versus AMPA receptors. J Neurosci. 1998;18:2423–36.

    PubMed  CAS  Google Scholar 

  136. Specht C, Izeddin I, Rodriguez PC, El Beheiry M, Rostaing P, Darzacq X, Dahan M, Triller A. Quantitative nanoscopy of inhibitory synapses: counting gephyrin molecules and receptor binding sites. Neuron. 2013;79:308–21.

    Article  PubMed  CAS  Google Scholar 

  137. Dejanovic B, Semtner M, Ebert S, Lamkemeyer T, Neuser F, Lüscher B, Meier JC, Schwarz G. Palmitoylation of gephyrin controls receptor clustering and plasticity of GABAergic synapses. PLoS Biol. 2014;12:e1001908.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  138. Wanaverbecq N, Semyanov A, Pavlov I, Walker MC, Kullmann DM. Cholinergic axons modulate GABAergic signaling among hippocampal interneurons via postsynaptic alpha 7 nicotinic receptors. J Neurosci. 2007;27:5683–93.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  139. Ji D, Dani JA. Inhibition and disinhibition of pyramidal neurons by activation of nicotinic receptors on hippocampal interneurons. J Neurophysiol. 2000;83:2682–90.

    PubMed  CAS  Google Scholar 

  140. Rosza B, Katona G, Kaszas A, Szipocs R, Vizi ES. Dendritic nicotinic receptors modulated backpropagating action potentials and long-term plasticity of interneurons. Eur J Neurosci. 2008;27:364–77.

    Article  Google Scholar 

  141. Dani JA, Bertrand D. Nicotinic acetylcholine receptors and nicotinic choliergic mechanisms of the central nervous system. Annu Rev Pharmacol Toxicol. 2007;47:699–729.

    Article  PubMed  CAS  Google Scholar 

  142. McCann CM, Tapia JC, Kim H, Coggan JS, Lichtman JW. Rapid and modifiable neurotransmitter receptor dynamics at a neuronal synapse in vivo. Nat Neurosci. 2008;11(7):807–15.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  143. Akaaboune M, Cullican SM, Turney SG, Lichtman JW. Rapid and reversible effect of activity on acetylcholine receptor density at the neuromuscular junction in vivo. Science. 1999;286:503–7.

    Article  PubMed  CAS  Google Scholar 

  144. Bruneau EG, Akaaboune M. The dynamics of recycled acetylcholine receptors at the neuromuscular junction in vivo. Development. 2006;133(22):4485–93.

    Article  PubMed  CAS  Google Scholar 

  145. Halff AW, Gómez-Varela D, John D, Berg DK. A novel mechanism for nicotinic potentiation of glutamatergic synapses. J Neurosci. 2014;34(6):2051–64.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  146. Fernandes CC, Berg DK, Gomez-Varela D. Lateral mobility of nicotinic acetylcholine receptors on neurons is determined by receptor composition, local domain, and cell type. J Neurosci. 2010;30(26):8841–51.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  147. Kass RS. The channelopathies: novel insights into molecular and genetic mechanisms of human disease. J Clin Invest. 2005;115:1986–9.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  148. Perez-Lloret S, Barrantes FJ. Deficits in cholinergic neurotransmission and their clinical correlates in Parkinson’s disease. NPJ Parkinsons Dis. 2016;2:16001.

    Article  PubMed  PubMed Central  Google Scholar 

  149. Remmers C, Sweet RA, Penzes P. Abnormal kalirin signaling in neuropsychiatric disorders. Brain Res Bull. 2014;103:29–38.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Experimental work quoted in this article was supported by grants PICT 2011-0604 from FONCYT, Ministry of Science and Technology and PIP No. N° 112-201101-01023 from the National Scientific and Technical Research Council of Argentina (CONICET).

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  1. Faculty of Medical Sciences, Laboratory of Molecular Neurobiology, Institute for Biomedical Research (BIOMED), UCA-CONICET, Av. Alicia Moreau de Justo 1600, C1107AFF, Buenos Aires, Argentina

    Francisco J. Barrantes

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  1. Centre for Cellular & Molecular Biology , Hyderabad, India

    Amitabha Chattopadhyay

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Barrantes, F.J. (2017). Spatiotemporal Dynamics of Nicotinic Acetylcholine Receptors and Lipid Platforms. In: Chattopadhyay, A. (eds) Membrane Organization and Dynamics . Springer Series in Biophysics, vol 20. Springer, Cham. https://doi.org/10.1007/978-3-319-66601-3_9

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