Skip to main content
SpringerLink
Log in

Ganglioside Microdomains on Cellular and Intracellular Membranes Regulate Neuronal Cell Fate Determination

  • Chapter
  • First Online:
Glycobiology of the Nervous System

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 29))

Abstract

Gangliosides are sialylated glycosphingolipids (GSLs) with essential but enigmatic functions in brain activities and neural stem cell (NSC) maintenance. Our group has pioneered research on the importance of gangliosides for growth factor receptor signaling and epigenetic regulation of NSC activity and differentiation. The primary localization of gangliosides is on cell-surface microdomains and the drastic dose and composition changes during neural differentiation strongly suggest that they are not only important as biomarkers, but also are involved in modulating NSC fate determination. Ganglioside GD3 is the predominant species in NSCs and GD3-synthase knockout (GD3S-KO) revealed reduction of postnatal NSC pools with severe behavioral deficits. Exogenous administration of GD3 significantly restored the NSC pools and enhanced the stemness of NSCs with multipotency and self-renewal. Since morphological changes during neurogenesis require a huge amount of energy, mitochondrial functions are vital for neurogenesis. We discovered that a mitochondrial fission protein, the dynamin-related protein-1 (Drp1), as a novel GD3-binding protein, and GD3 regulates mitochondrial dynamics. Furthermore, we discovered that GM1 ganglioside promotes neuronal differentiation by an epigenetic regulatory mechanism. Nuclear GM1 binds with acetylated histones on the promoters of N-acetylgalactosaminyltransferase (GalNAcT; GM2 synthase) as well as on the NeuroD1 genes in differentiated neurons. In addition, epigenetic activation of the GalNAcT gene was detected as accompanied by an apparent induction of neuronal differentiation in NSCs responding to an exogenous supplement of GM1. GM1 is indeed localized in the nucleus where it can interact with transcriptionally active histones. Interestingly, GM1 could induce epigenetic activation of the tyrosine hydroxylase (TH) gene, with recruitment of nuclear receptor related 1 (Nurr1, also known as NR4A2), a dopaminergic neuron-associated transcription factor, to the TH promoter region. In this way, GM1 epigenetically regulates dopaminergic neuron specific gene expression. GM1 interacts with active chromatin via acetylated histones to recruit transcription factors at the nuclear periphery, resulting in changes in gene expression for neuronal differentiation. The significance is that multifunctional gangliosides modulate lipid microdomains to regulate functions of important molecules on multiple sites: the plasma membrane, mitochondrial membrane, and nuclear membrane. Versatile gangliosides could regulate functional neurons as well as sustain NSC functions via modulating protein and gene activities on ganglioside microdomains.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AP-2:

Activating protein 2

BrdU:

Bromodeoxyuridine

Cer:

Ceramide

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

DCX:

Doublecortin

Drp1:

Dynamin related protein-1

EGFR:

Epidermal growth factor receptor

GalCer:

Galactosylceramide

GalNAcT:

N-acetylgalactosaminyltransferase

GD3:

Disialoganglioside 3

GD3S:

GD3 synthase

GFAP:

Glial fibrillary acidic protein

GlcCer:

Glucosylceramide

GM1:

Monosialoganglioside 1

GM2S:

GM2 synthase

GM3S:

GM3 synthase

GSL:

Glycosphingolipid

GT:

Glycosyltransferase

LacCer:

Lactosylceramide

MS:

Mass spectrometry

NEC:

Neuroepithelial cell

NPC:

Neural progenitor cell

NSC:

Neural stem cell

Nurr1:

Nuclear receptor related 1, also known as NR4A2

PDGF:

Platelet-derived growth factor

PLA:

Proximity Ligation Assay

PSA-NCAM:

Polysialic acid-neural cell adhesion molecule

RGC:

Radial glial cell

SGZ:

Subgranular zone

SOX2:

SRY (sex determining region Y)-box 2

Sp1:

Specificity protein 1

ST:

Sialyltransferase

SVZ:

Subventricular zone

TH:

Tyrosine hydroxylase

References

  • Ando S. Glycoconjugate changes in aging and age-related diseases. Adv Neurobiol. 2014;9:415–47.

    Article  PubMed  Google Scholar 

  • Ando S, Yu RK. Isolation and characterization of two isomers of brain tetrasialogangliosides. J Biol Chem. 1979;254:12224–9.

    Article  CAS  PubMed  Google Scholar 

  • Ando S, Hirabayashi Y, Kon K, Inagaki F, Tate S, Whittaker VP. A trisialoganglioside containing a sialyl alpha 2-6 N-acetylgalactosamine residue is a cholinergic-specific antigen, Chol-1 alpha. J Biochem. 1992;111:287–90.

    Article  CAS  PubMed  Google Scholar 

  • Ando S, Tanaka Y, Waki H, Kon K, Iwamoto M, Fukui F. Gangliosides and sialylcholesterol as modulators of synaptic functions. Ann N Y Acad Sci. 1998;845:232–9.

    Article  CAS  PubMed  Google Scholar 

  • Ando S, Tanaka Y, Kobayashi S, Fukui F, Iwamoto M, Waki H, Tai T, Hirabayashi Y. Synaptic function of cholinergic-specific Chol-1alpha ganglioside. Neurochem Res. 2004;29:857–67.

    Article  CAS  PubMed  Google Scholar 

  • Beckervordersandforth R, Ebert B, Schaffner I, Moss J, Fiebig C, Shin J, Moore DL, Ghosh L, Trinchero MF, Stockburger C, et al. Role of mitochondrial metabolism in the control of early lineage progression and aging phenotypes in adult hippocampal neurogenesis. Neuron. 2017;93:560–573 e566.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boukhris A, Schule R, Loureiro JL, Lourenco CM, Mundwiller E, Gonzalez MA, Charles P, Gauthier J, Rekik I, Acosta Lebrigio RF, et al. Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. Am J Hum Genet. 2013;93:118–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bremer EG, Schlessinger J, Hakomori S. Ganglioside-mediated modulation of cell growth. Specific effects of GM3 on tyrosine phosphorylation of the epidermal growth factor receptor. J Biol Chem. 1986;261:2434–40.

    Article  CAS  PubMed  Google Scholar 

  • Carlen M, Meletis K, Goritz C, Darsalia V, Evergren E, Tanigaki K, Amendola M, Barnabe-Heider F, Yeung MS, Naldini L, et al. Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke. Nat Neurosci. 2009;12:259–67.

    Article  CAS  PubMed  Google Scholar 

  • Chiasson BJ, Tropepe V, Morshead CM, van der Kooy D. Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential, but only subependymal cells have neural stem cell characteristics. J Neurosci. 1999;19:4462–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coskun V, Wu H, Blanchi B, Tsao S, Kim K, Zhao J, Biancotti JC, Hutnick L, Krueger RC Jr, Fan G, et al. CD133+ neural stem cells in the ependyma of mammalian postnatal forebrain. Proc Natl Acad Sci U S A. 2008;105:1026–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Delgado AC, Maldonado-Soto AR, Silva-Vargas V, Mizrak D, von Kanel T, Tan KR, Paul A, Madar A, Cuervo H, Kitajewski J, et al. Release of stem cells from quiescence reveals gliogenic domains in the adult mouse brain. Science. 2021;372:1205–9.

    Article  CAS  PubMed  Google Scholar 

  • Derrington EA, Borroni E. The developmental expression of the cholinergic-specific antigen Chol-1 in the central and peripheral nervous system of the rat. Brain Res Dev Brain Res. 1990;52:131–40.

    Article  CAS  PubMed  Google Scholar 

  • Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci. 1997;17:5046–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell. 1999;97:703–16.

    Article  CAS  PubMed  Google Scholar 

  • Eisenbarth GS, Walsh FS, Nirenberg M. Monoclonal antibody to a plasma membrane antigen of neurons. Proc Natl Acad Sci U S A. 1979;76:4913–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Encinas JM, Vaahtokari A, Enikolopov G. Fluoxetine targets early progenitor cells in the adult brain. Proc Natl Acad Sci U S A. 2006;103:8233–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferrari G, Fabris M, Gorio A. Gangliosides enhance neurite outgrowth in PC12 cells. Brain Res. 1983;284:215–21.

    Article  CAS  PubMed  Google Scholar 

  • Filippov V, Kronenberg G, Pivneva T, Reuter K, Steiner B, Wang LP, Yamaguchi M, Kettenmann H, Kempermann G. Subpopulation of nestin-expressing progenitor cells in the adult murine hippocampus shows electrophysiological and morphological characteristics of astrocytes. Mol Cell Neurosci. 2003;23:373–82.

    Article  CAS  PubMed  Google Scholar 

  • Freischutz B, Saito M, Rahmann H, Yu RK. Activities of five different sialyltransferases in fish and rat brains. J Neurochem. 1994;62:1965–73.

    Article  CAS  PubMed  Google Scholar 

  • Freischutz B, Saito M, Rahmann H, Yu RK. Characterization of sialyltransferase-IV activity and its involvement in the c-pathway of brain ganglioside metabolism. J Neurochem. 1995;64:385–93.

    Article  CAS  PubMed  Google Scholar 

  • Furukawa K, Ohmi Y, Ohkawa Y, Tajima O, Furukawa K. Glycosphingolipids in the regulation of the nervous system. Adv Neurobiol. 2014;9:307–20.

    Article  PubMed  Google Scholar 

  • Hadaczek P, Wu G, Sharma N, Ciesielska A, Bankiewicz K, Davidow AL, Lu ZH, Forsayeth J, Ledeen RW. GDNF signaling implemented by GM1 ganglioside; failure in Parkinson's disease and GM1-deficient murine model. Exp Neurol. 2015;263:177–89.

    Article  CAS  PubMed  Google Scholar 

  • Hanai N, Nores GA, MacLeod C, Torres-Mendez CR, Hakomori S. Ganglioside-mediated modulation of cell growth. Specific effects of GM3 and lyso-GM3 in tyrosine phosphorylation of the epidermal growth factor receptor. J Biol Chem. 1988;263:10915–21.

    Article  CAS  PubMed  Google Scholar 

  • Hirabayashi Y, Nakao T, Irie F, Whittaker VP, Kon K, Ando S. Structural characterization of a novel cholinergic neuron-specific ganglioside in bovine brain. J Biol Chem. 1992;267:12973–8.

    Article  CAS  PubMed  Google Scholar 

  • Hong JM, Jeon H, Choi YC, Cho H, Hong YB, Park HJ. A compound heterozygous pathogenic variant in B4GALNT1 is associated with axonal Charcot-Marie-tooth disease. J Clin Neurol. 2021;17:534–40.

    Article  PubMed  PubMed Central  Google Scholar 

  • Inoko E, Nishiura Y, Tanaka H, Takahashi T, Furukawa K, Kitajima K, Sato C. Developmental stage-dependent expression of an alpha2,8-trisialic acid unit on glycoproteins in mouse brain. Glycobiology. 2010;20:916–28.

    Article  CAS  PubMed  Google Scholar 

  • Itokazu Y, Yu RK. Amyloid beta-peptide 1-42 modulates the proliferation of mouse neural stem cells: upregulation of fucosyltransferase IX and notch signaling. Mol Neurobiol. 2014;50(1):186–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Itokazu Y, Pagano RE, Schroeder AS, O'Grady SM, Limper AH, Marks DL. Reduced GM1 ganglioside in CFTR-deficient human airway cells results in decreased beta1-integrin signaling and delayed wound repair. Am J Physiol Cell Physiol. 2014;306:C819–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Itokazu Y, Tajima N, Kerosuo L, Somerharju P, Sariola H, Yu RK, Kakela R. A2B5+/GFAP+ cells of rat spinal cord share a similar lipid profile with progenitor cells: a comparative lipidomic study. Neurochem Res. 2016a;41(7):1527–44.

    Article  CAS  PubMed  Google Scholar 

  • Itokazu Y, Tsai YT, Yu RK. Epigenetic regulation of ganglioside expression in neural stem cells and neuronal cells. Glycoconj J. 2016b;34(6):749–56.

    Article  PubMed  PubMed Central  Google Scholar 

  • Itokazu Y, Wang J, Yu RK. Gangliosides in nerve cell specification. Prog Mol Biol Transl Sci. 2018;156:241–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Itokazu Y, Li D, Yu RK. Intracerebroventricular infusion of gangliosides augments the adult neural stem cell Pool in mouse brain. ASN Neuro. 2019;11:1759091419884859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Itokazu Y, Fuchigami T, Morgan JC, Yu RK. Intranasal infusion of GD3 and GM1 gangliosides downregulates alpha-synuclein and controls tyrosine hydroxylase gene in a PD model mouse. Mol Ther. 2021;29:3059–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J. Identification of a neural stem cell in the adult mammalian central nervous system. Cell. 1999;96:25–34.

    Article  CAS  PubMed  Google Scholar 

  • Kasai N, Yu RK. The monoclonal antibody A2B5 is specific to ganglioside GQ1c. Brain Res. 1983;277:155–8.

    Article  CAS  PubMed  Google Scholar 

  • Kawai H, Allende ML, Wada R, Kono M, Sango K, Deng C, Miyakawa T, Crawley JN, Werth N, Bierfreund U, et al. Mice expressing only monosialoganglioside GM3 exhibit lethal audiogenic seizures. J Biol Chem. 2001;276:6885–8.

    Article  CAS  PubMed  Google Scholar 

  • Kishimoto N, Shimizu K, Sawamoto K. Neuronal regeneration in a zebrafish model of adult brain injury. Dis Model Mech. 2012;5:200–9.

    Article  CAS  PubMed  Google Scholar 

  • Kong JN, Zhu Z, Itokazu Y, Wang G, Dinkins MB, Zhong L, Lin HP, Elsherbini A, Leanhart S, Jiang X, et al. Novel function of ceramide for regulation of mitochondrial ATP release in astrocytes. J Lipid Res. 2018;59:488–506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koon NA, Itokazu Y, Yu RK. Ganglioside-dependent neural stem cell proliferation in Alzheimer's disease model mice. ASN Neuro. 2015;7

    Google Scholar 

  • Kumagai T, Tanaka M, Yokoyama M, Sato T, Shinkai T, Furukawa K. Early lethality of beta-1,4-galactosyltransferase V-mutant mice by growth retardation. Biochem Biophys Res Commun. 2009;379:456–9.

    Article  CAS  PubMed  Google Scholar 

  • Laywell ED, Rakic P, Kukekov VG, Holland EC, Steindler DA. Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proc Natl Acad Sci U S A. 2000;97:13883–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ledeen RW, Wu G. The multi-tasked life of GM1 ganglioside, a true factotum of nature. Trends Biochem Sci. 2015;40:407–18.

    Article  CAS  PubMed  Google Scholar 

  • Ledeen RW, Wu G. Gangliosides, alpha-Synuclein, and Parkinson's disease. Prog Mol Biol Transl Sci. 2018;156:435–54.

    Article  CAS  PubMed  Google Scholar 

  • Lee JS, Yoo Y, Lim BC, Kim KJ, Song J, Choi M, Chae JH. GM3 synthase deficiency due to ST3GAL5 variants in two Korean female siblings: masquerading as Rett syndrome-like phenotype. Am J Med Genet A. 2016;70(8):2200–5.

    Article  Google Scholar 

  • Lugert S, Vogt M, Tchorz JS, Muller M, Giachino C, Taylor V. Homeostatic neurogenesis in the adult hippocampus does not involve amplification of Ascl1(high) intermediate progenitors. Nat Commun. 2012;3:670.

    Article  PubMed  Google Scholar 

  • Morshead CM. Adult neural stem cells: attempting to solve the identity crisis. Dev Neurosci. 2004;26:93–100.

    Article  CAS  PubMed  Google Scholar 

  • Nakatani Y, Yanagisawa M, Suzuki Y, Yu RK. Characterization of GD3 ganglioside as a novel biomarker of mouse neural stem cells. Glycobiology. 2010;20:78–86.

    Article  CAS  PubMed  Google Scholar 

  • Ngamukote S, Yanagisawa M, Ariga T, Ando S, Yu RK. Developmental changes of glycosphingolipids and expression of glycogenes in mouse brains. J Neurochem. 2007;103:2327–41.

    Article  CAS  PubMed  Google Scholar 

  • Nguyen L, McCord KA, Bui DT, Bouwman KM, Kitova EN, Elaish M, Kumawat D, Daskhan GC, Tomris I, Han L, et al. Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2. Nat Chem Biol. 2021;18(1):81–90.

    Article  PubMed  Google Scholar 

  • Nishie T, Hikimochi Y, Zama K, Fukusumi Y, Ito M, Yokoyama H, Naruse C, Ito M, Asano M. Beta4-galactosyltransferase-5 is a lactosylceramide synthase essential for mouse extra-embryonic development. Glycobiology. 2010;20:1311–22.

    Article  CAS  PubMed  Google Scholar 

  • Palazzo AF, Eng CH, Schlaepfer DD, Marcantonio EE, Gundersen GG. Localized stabilization of microtubules by integrin- and FAK-facilitated Rho signaling. Science. 2004;303:836–9.

    Article  CAS  PubMed  Google Scholar 

  • Prendergast J, Umanah GK, Yoo SW, Lagerlof O, Motari MG, Cole RN, Huganir RL, Dawson TM, Dawson VL, Schnaar RL. Ganglioside regulation of AMPA receptor trafficking. J Neurosci. 2014;34:13246–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raff MC, Abney ER, Cohen J, Lindsay R, Noble M. Two types of astrocytes in cultures of developing rat white matter: differences in morphology, surface gangliosides, and growth characteristics. J Neurosci. 1983;3:1289–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosner H, Greis C, Henke-Fahle S. Developmental expression in embryonic rat and chicken brain of a polysialoganglioside-antigen reacting with the monoclonal antibody Q 211. Brain Res. 1988;470:161–71.

    Article  CAS  PubMed  Google Scholar 

  • Saito M, Kitamura H, Sugiyama K. The specificity of monoclonal antibody A2B5 to c-series gangliosides. J Neurochem. 2001;78:64–74.

    Article  CAS  PubMed  Google Scholar 

  • Schwartz M, Spirman N. Sprouting from chicken embryo dorsal root ganglia induced by nerve growth factor is specifically inhibited by affinity-purified antiganglioside antibodies. Proc Natl Acad Sci U S A. 1982;79:6080–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seri B, Garcia-Verdugo JM, McEwen BS, Alvarez-Buylla A. Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci. 2001;21:7153–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simpson MA, Cross H, Proukakis C, Priestman DA, Neville DC, Reinkensmeier G, Wang H, Wiznitzer M, Gurtz K, Verganelaki A, et al. Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase. Nat Genet. 2004;36:1225–9.

    Article  CAS  PubMed  Google Scholar 

  • Son G, Han J. Roles of mitochondria in neuronal development. BMB Rep. 2018;51:549–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steiner B, Klempin F, Wang L, Kott M, Kettenmann H, Kempermann G. Type-2 cells as link between glial and neuronal lineage in adult hippocampal neurogenesis. Glia. 2006;54:805–14.

    Article  PubMed  Google Scholar 

  • Steinman RM, Mellman IS, Muller WA, Cohn ZA. Endocytosis and the recycling of plasma membrane. J Cell Biol. 1983;96:1–27.

    Article  CAS  PubMed  Google Scholar 

  • Suhonen JO, Peterson DA, Ray J, Gage FH. Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo. Nature. 1996;383:624–7.

    Article  CAS  PubMed  Google Scholar 

  • Suzuki Y, Yanagisawa M, Ariga T, Yu RK. Histone acetylation-mediated glycosyltransferase gene regulation in mouse brain during development. J Neurochem. 2011;116:874–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Svennerholm L. Chromatographic separation of human brain gangliosides. J Neurochem. 1963;10:613–23.

    Article  CAS  PubMed  Google Scholar 

  • Tang FL, Wang J, Itokazu Y, Yu RK. Enhanced susceptibility to chemoconvulsant-induced seizures in ganglioside GM3 synthase knockout mice. ASN Neuro. 2020a;12:1759091420938175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang FL, Wang J, Itokazu Y, Yu RK. Ganglioside GD3 regulates dendritic growth in newborn neurons in adult mouse hippocampus via modulation of mitochondrial dynamics. J Neurochem. 2020b;156(6):819–33.

    Article  PubMed  PubMed Central  Google Scholar 

  • The nomenclature of lipids. Recommendations (1976) IUPAC-IUB commission on biochemical nomenclature. Lipids. 1977;12:455–68.

    Google Scholar 

  • Tsai YT, Yu RK. Epigenetic activation of mouse ganglioside synthase genes: implications for neurogenesis. J Neurochem. 2014;128:101–10.

    Article  CAS  PubMed  Google Scholar 

  • Tsai YT, Itokazu Y, Yu RK. GM1 ganglioside is involved in epigenetic activation loci of neuronal cells. Neurochem Res. 2016;41:107–15.

    Article  CAS  PubMed  Google Scholar 

  • Tsuji S, Arita M, Nagai Y. GQ1b, a bioactive ganglioside that exhibits novel nerve growth factor (NGF)-like activities in the two neuroblastoma cell lines. J Biochem. 1983;94:303–6.

    Article  CAS  PubMed  Google Scholar 

  • Viljetic B, Labak I, Majic S, Stambuk A, Heffer M. Distribution of mono-, di- and trisialo gangliosides in the brain of Actinopterygian fishes. Biochim Biophys Acta. 2012;1820:1437–43.

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Yu RK. Interaction of ganglioside GD3 with an EGF receptor sustains the self-renewal ability of mouse neural stem cells in vitro. Proc Natl Acad Sci U S A. 2013;110:19137–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Cheng A, Wakade C, Yu RK. Ganglioside GD3 is required for neurogenesis and long-term maintenance of neural stem cells in the postnatal mouse brain. J Neurosci. 2014;34:13790–800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu G, Lu ZH, Obukhov AG, Nowycky MC, Ledeen RW. Induction of calcium influx through TRPC5 channels by cross-linking of GM1 ganglioside associated with alpha5beta1 integrin initiates neurite outgrowth. J Neurosci. 2007;27:7447–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu G, Lu ZH, Kulkarni N, Ledeen RW. Deficiency of ganglioside GM1 correlates with Parkinson's disease in mice and humans. J Neurosci Res. 2012;90:1997–2008.

    Article  CAS  PubMed  Google Scholar 

  • Wu G, Lu ZH, Seo JH, Alselehdar SK, DeFrees S, Ledeen RW. Mice deficient in GM1 manifest both motor and non-motor symptoms of Parkinson's disease; successful treatment with synthetic GM1 ganglioside. Exp Neurol. 2020;329:113284.

    Article  CAS  PubMed  Google Scholar 

  • Yamashita T, Wada R, Sasaki T, Deng C, Bierfreund U, Sandhoff K, Proia RL. A vital role for glycosphingolipid synthesis during development and differentiation. Proc Natl Acad Sci U S A. 1999;96:9142–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamashita T, Wu YP, Sandhoff R, Werth N, Mizukami H, Ellis JM, Dupree JL, Geyer R, Sandhoff K, Proia RL. Interruption of ganglioside synthesis produces central nervous system degeneration and altered axon-glial interactions. Proc Natl Acad Sci U S A. 2005;102:2725–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu RK, Ando S. Structures of some new complex gangliosides of fish brain. Adv Exp Med Biol. 1980;125:33–45.

    Article  CAS  PubMed  Google Scholar 

  • Yu RK, Itokazu Y. Glycolipid and glycoprotein expression during neural development. Adv Neurobiol. 2014;9:185–222.

    Article  PubMed  Google Scholar 

  • Yu RK, Yanagisawa M. Glycosignaling in neural stem cells: involvement of glycoconjugates in signal transduction modulating the neural stem cell fate. J Neurochem. 2007;103 Suppl 1:39–46.

    Article  PubMed  Google Scholar 

  • Yu RK, Nakatani Y, Yanagisawa M. The role of glycosphingolipid metabolism in the developing brain. J Lipid Res. 2009;50 Suppl:S440–5.

    Article  PubMed  Google Scholar 

  • Yu RK, Tsai YT, Ariga T, Yanagisawa M. Structures, biosynthesis, and functions of gangliosides–an overview. J Oleo Sci. 2011;60:537–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Conflict of Interest

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA

    Yutaka Itokazu & Robert K. Yu

Authors
  1. Yutaka Itokazu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert K. Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert K. Yu .

Editor information

Editors and Affiliations

  1. Biochemistry and Molecular Biology, The Pennsylvania State University, Hershey, PA, USA

    Cara-Lynne Schengrund

  2. Department of Neuroscience and Regenerative Medicine, Medical College of Georgia Augusta University, Augusta, GA, USA

    Robert K. Yu

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Itokazu, Y., Yu, R.K. (2023). Ganglioside Microdomains on Cellular and Intracellular Membranes Regulate Neuronal Cell Fate Determination. In: Schengrund, CL., Yu, R.K. (eds) Glycobiology of the Nervous System. Advances in Neurobiology, vol 29. Springer, Cham. https://doi.org/10.1007/978-3-031-12390-0_10

Download citation

Publish with us

Policies and ethics

Search

Navigation