Skip to main content
SpringerLink
Log in

Cell adhesion molecule control of planar spindle orientation

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Polarized epithelial cells align the mitotic spindle in the plane of the sheet to maintain tissue integrity and to prevent malignant transformation. The orientation of the spindle apparatus is regulated by the immobilization of the astral microtubules at the lateral cortex and depends on the precise localization of the dynein–dynactin motor protein complex which captures microtubule plus ends and generates pulling forces towards the centrosomes. Recent developments indicate that signals derived from intercellular junctions are required for the stable interaction of the dynein–dynactin complex with the cortex. Here, we review the molecular mechanisms that regulate planar spindle orientation in polarized epithelial cells and we illustrate how different cell adhesion molecules through distinct and non-overlapping mechanisms instruct the cells to align the mitotic spindle in the plane of the sheet.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

AJ:

Adherens junctions

Antxr2:

Anthrax toxin receptor 2

APC:

Adenomatous polyposis coli

Arp:

Actin-related protein

βPIX:

PAK-interacting exchange factor β

Cdc42:

Cell division cycle 42

Dia1:

Diaphanous-related formin 1

EB1:

End-binding protein 1

Ect2:

Epithelial cell transforming 2

ERM:

Ezrin, radixin, moesin

ERMAD:

ERM-association domain

FERM:

4.1 protein and ERM

GAP:

GTPase-activating protein

GEF:

Guanine nucleotide exchange factor

JAM:

Junctional adhesion molecule

LGN:

Leu-Gly-Asn repeat-enriched protein

MDCK:

Madin–Darby canine kidney

MT:

Microtubule

NuMA:

Nuclear mitotic apparatus

PAK2:

p21-activated kinase 2

Par:

Partitioning defective

PDZ:

PSD95–Discs large–ZO-1

PI(3)K:

Phosphoinositide 3-kinase

PtdIns:

Phosphatidylinositol

RCC1:

Regulator of chromatin condensation 1

SLK:

Sterile 20-like kinase

TJ:

Tight junctions

References

  1. Morin X, Bellaiche Y (2011) Mitotic spindle orientation in asymmetric and symmetric cell divisions during animal development. Dev Cell 21(1):102–119

    Article  CAS  PubMed  Google Scholar 

  2. Lechler T, Fuchs E (2005) Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature 437(7056):275–280

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Wu M, Smith CL, Hall JA, Lee I, Luby-Phelps K, Tallquist MD (2010) Epicardial spindle orientation controls cell entry into the myocardium. Dev Cell 19(1):114–125. doi:10.1016/j.devcel.2010.06.011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Minc N, Burgess D, Chang F (2011) Influence of cell geometry on division-plane positioning. Cell 144(3):414–426. doi:10.1016/j.cell.2011.01.016

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Kiyomitsu T, Cheeseman IM (2012) Chromosome- and spindle-pole-derived signals generate an intrinsic code for spindle position and orientation. Nat Cell Biol 14(3):311–317

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Bird SL, Heald R, Weis K (2013) RanGTP and CLASP1 cooperate to position the mitotic spindle. Mol Biol Cell 24(16):2506–2514. doi:10.1091/mbc.E13-03-0150

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Wu J, Mlodzik M (2008) The frizzled extracellular domain is a ligand for Van Gogh/Stbm during nonautonomous planar cell polarity signaling. Dev Cell 15(3):462–469. doi:10.1016/j.devcel.2008.08.004

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Thery M, Racine V, Pepin A, Piel M, Chen Y, Sibarita JB, Bornens M (2005) The extracellular matrix guides the orientation of the cell division axis. Nat Cell Biol 7(10):947–953

    Article  CAS  PubMed  Google Scholar 

  9. Toyoshima F, Nishida E (2007) Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1- and myosin X-dependent manner. EMBO J 26(6):1487–1498

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Goldstein B (1995) Cell contacts orient some cell division axes in the Caenorhabditis elegans embryo. J Cell Biol 129(4):1071–1080

    Article  CAS  PubMed  Google Scholar 

  11. Dujardin DL, Vallee RB (2002) Dynein at the cortex. Curr Opin Cell Biol 14(1):44–49

    Article  CAS  PubMed  Google Scholar 

  12. Kardon JR, Vale RD (2009) Regulators of the cytoplasmic dynein motor. Nat Rev Mol Cell Biol 10(12):854–865

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Busson S, Dujardin D, Moreau A, Dompierre J, De Mey JR (1998) Dynein and dynactin are localized to astral microtubules and at cortical sites in mitotic epithelial cells. Curr Biol 8(9):541–544

    Article  CAS  PubMed  Google Scholar 

  14. Moore JK, Cooper JA (2010) Coordinating mitosis with cell polarity: molecular motors at the cell cortex. Semin Cell Dev Biol 21(3):283–289

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Markus SM, Lee WL (2011) Microtubule-dependent path to the cell cortex for cytoplasmic dynein in mitotic spindle orientation. Bioarchitecture 1(5):209–215

    Article  PubMed Central  PubMed  Google Scholar 

  16. Markus SM, Lee WL (2011) Regulated offloading of cytoplasmic dynein from microtubule plus ends to the cortex. Dev Cell 20(5):639–651. doi:10.1016/j.devcel.2011.04.011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Grill SW, Howard J, Schaffer E, Stelzer EH, Hyman AA (2003) The distribution of active force generators controls mitotic spindle position. Science 301(5632):518–521. doi:10.1126/science.1086560

    Article  CAS  PubMed  Google Scholar 

  18. Laan L, Pavin N, Husson J, Romet-Lemonne G, van Duijn M, Lopez MP, Vale RD, Julicher F, Reck-Peterson SL, Dogterom M (2012) Cortical dynein controls microtubule dynamics to generate pulling forces that position microtubule asters. Cell 148(3):502–514

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Stevermann L, Liakopoulos D (2012) Molecular mechanisms in spindle positioning: structures and new concepts. Curr Opin Cell Biol 24(6):816–824. doi:10.1016/j.ceb.2012.10.005

    Article  CAS  PubMed  Google Scholar 

  20. Kotak S, Gonczy P (2013) Mechanisms of spindle positioning: cortical force generators in the limelight. Curr Opin Cell Biol 25(6):741–748. doi:10.1016/j.ceb.2013.07.008

    Article  CAS  PubMed  Google Scholar 

  21. Compton DA, Szilak I, Cleveland DW (1992) Primary structure of NuMA, an intranuclear protein that defines a novel pathway for segregation of proteins at mitosis. J Cell Biol 116(6):1395–1408

    Article  CAS  PubMed  Google Scholar 

  22. Kotak S, Busso C, Gonczy P (2012) Cortical dynein is critical for proper spindle positioning in human cells. J Cell Biol 199(1):97–110. doi:10.1083/jcb.201203166

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Du Q, Stukenberg PT, Macara IG (2001) A mammalian partner of inscuteable binds NuMA and regulates mitotic spindle organization. Nat Cell Biol 3(12):1069–1075. doi:10.1038/ncb1201-1069

    Article  CAS  PubMed  Google Scholar 

  24. Du Q, Macara IG (2004) Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell 119(4):503–516

    Article  CAS  PubMed  Google Scholar 

  25. Zheng Z, Zhu H, Wan Q, Liu J, Xiao Z, Siderovski DP, Du Q (2010) LGN regulates mitotic spindle orientation during epithelial morphogenesis. J Cell Biol 189(2):275–288

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Joberty G, Petersen C, Gao L, Macara IG (2000) The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nat Cell Biol 2(8):531–539

    Article  CAS  PubMed  Google Scholar 

  27. Lin D, Edwards AS, Fawcett JP, Mbamalu G, Scott JD, Pawson T (2000) A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity. Nat Cell Biol 2(8):540–547

    Article  CAS  PubMed  Google Scholar 

  28. Chen X, Macara IG (2005) Par-3 controls tight junction assembly through the Rac exchange factor Tiam1. Nat Cell Biol 7(3):262–269

    Article  CAS  PubMed  Google Scholar 

  29. Hirose T, Izumi Y, Nagashima Y, Tamai-Nagai Y, Kurihara H, Sakai T, Suzuki Y, Yamanaka T, Suzuki A, Mizuno K, Ohno S (2002) Involvement of ASIP/PAR-3 in the promotion of epithelial tight junction formation. J Cell Sci 115(Pt 12):2485–2495

    CAS  PubMed  Google Scholar 

  30. Suzuki A, Ishiyama C, Hashiba K, Shimizu M, Ebnet K, Ohno S (2002) aPKC kinase activity is required for the asymmetric differentiation of the premature junctional complex during epithelial cell polarization. J Cell Sci 115(Pt 18):3565–3573

    Article  CAS  PubMed  Google Scholar 

  31. Nagai-Tamai Y, Mizuno K, Hirose T, Suzuki A, Ohno S (2002) Regulated protein-protein interaction between aPKC and PAR-3 plays an essential role in the polarization of epithelial cells. Genes Cells 7(11):1161–1171

    Article  CAS  PubMed  Google Scholar 

  32. Qin Y, Meisen WH, Hao Y, Macara IG (2010) Tuba, a Cdc42 GEF, is required for polarized spindle orientation during epithelial cyst formation. J Cell Biol 189(4):661–669

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Durgan J, Kaji N, Jin D, Hall A (2011) Par6B and atypical PKC (aPKC) regulate mitotic spindle orientation during epithelial morphogenesis. J Biol Chem 286(14):12461–12471

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Hao Y, Du Q, Chen X, Zheng Z, Balsbaugh JL, Maitra S, Shabanowitz J, Hunt DF, Macara IG (2010) Par3 controls epithelial spindle orientation by aPKC-mediated phosphorylation of apical pins. Curr Biol 20(20):1809–1818

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Hao Y, Macara IG (2008) Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1. J Cell Biol 182(5):827–836. doi:10.1083/jcb.200803110

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Reinsch S, Karsenti E (1994) Orientation of spindle axis and distribution of plasma membrane proteins during cell division in polarized MDCKII cells. J Cell Biol 126(6):1509–1526

    Article  CAS  PubMed  Google Scholar 

  37. Rosenblatt J, Cramer LP, Baum B, McGee KM (2004) Myosin II-dependent cortical movement is required for centrosome separation and positioning during mitotic spindle assembly. Cell 117(3):361–372

    Article  CAS  PubMed  Google Scholar 

  38. Baker J, Garrod D (1993) Epithelial cells retain junctions during mitosis. J Cell Sci 104(Pt 2):415–425

    PubMed  Google Scholar 

  39. Redemann S, Pecreaux J, Goehring NW, Khairy K, Stelzer EH, Hyman AA, Howard J (2010) Membrane invaginations reveal cortical sites that pull on mitotic spindles in one-cell C. elegans embryos. PLoS ONE 5(8):e12301. doi:10.1371/journal.pone.0012301

    Article  PubMed Central  PubMed  Google Scholar 

  40. Mitsushima M, Toyoshima F, Nishida E (2009) Dual role of Cdc42 in spindle orientation control of adherent cells. Mol Cell Biol 29(10):2816–2827. doi:10.1128/MCB.01713-08

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Campellone KG, Welch MD (2010) A nucleator arms race: cellular control of actin assembly. Nat Rev Mol Cell Biol 11(4):237–251. doi:10.1038/nrm2867

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Bovellan M, Romeo Y, Biro M, Boden A, Chugh P, Yonis A, Vaghela M, Fritzsche M, Moulding D, Thorogate R, Jegou A, Thrasher AJ, Romet-Lemonne G, Roux PP, Paluch EK, Charras G (2014) Cellular control of cortical actin nucleation. Curr Biol 24(14):1628–1635. doi:10.1016/j.cub.2014.05.069

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Rosa A, Vlassaks E, Pichaud F, Baum B (2015) Ect2/Pbl acts via Rho and polarity proteins to direct the assembly of an isotropic actomyosin cortex upon mitotic entry. Dev Cell 32(5):604–616. doi:10.1016/j.devcel.2015.01.012

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Matthews HK, Delabre U, Rohn JL, Guck J, Kunda P, Baum B (2012) Changes in Ect2 localization couple actomyosin-dependent cell shape changes to mitotic progression. Dev Cell 23(2):371–383. doi:10.1016/j.devcel.2012.06.003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Otomo T, Otomo C, Tomchick DR, Machius M, Rosen MK (2005) Structural basis of Rho GTPase-mediated activation of the formin mDia1. Mol Cell 18(3):273–281. doi:10.1016/j.molcel.2005.04.002

    Article  CAS  PubMed  Google Scholar 

  46. Fehon RG, McClatchey AI, Bretscher A (2010) Organizing the cell cortex: the role of ERM proteins. Nat Rev Mol Cell Biol 11(4):276–287. doi:10.1038/nrm2866

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Carreno S, Kouranti I, Glusman ES, Fuller MT, Echard A, Payre F (2008) Moesin and its activating kinase Slik are required for cortical stability and microtubule organization in mitotic cells. J Cell Biol 180(4):739–746. doi:10.1083/jcb.200709161

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Kunda P, Pelling AE, Liu T, Baum B (2008) Moesin controls cortical rigidity, cell rounding, and spindle morphogenesis during mitosis. Curr Biol 18(2):91–101. doi:10.1016/j.cub.2007.12.051

    Article  CAS  PubMed  Google Scholar 

  49. Machicoane M, de Frutos CA, Fink J, Rocancourt M, Lombardi Y, Garel S, Piel M, Echard A (2014) SLK-dependent activation of ERMs controls LGN-NuMA localization and spindle orientation. J Cell Biol 205(6):791–799. doi:10.1083/jcb.201401049

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Solinet S, Mahmud K, Stewman SF, Ben El Kadhi K, Decelle B, Talje L, Ma A, Kwok BH, Carreno S (2013) The actin-binding ERM protein Moesin binds to and stabilizes microtubules at the cell cortex. J Cell Biol 202(2):251–260. doi:10.1083/jcb.201304052

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Zhu J, Wen W, Zheng Z, Shang Y, Wei Z, Xiao Z, Pan Z, Du Q, Wang W, Zhang M (2011) LGN/mInsc and LGN/NuMA complex structures suggest distinct functions in asymmetric cell division for the Par3/mInsc/LGN and Galphai/LGN/NuMA pathways. Mol Cell 43(3):418–431

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Williams SE, Ratliff LA, Postiglione MP, Knoblich JA, Fuchs E (2014) Par3-mInsc and Galphai3 cooperate to promote oriented epidermal cell divisions through LGN. Nat Cell Biol 16(8):758–769. doi:10.1038/ncb3001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Toyoshima F, Matsumura S, Morimoto H, Mitsushima M, Nishida E (2007) PtdIns(3,4,5)P3 regulates spindle orientation in adherent cells. Dev Cell 13(6):796–811

    Article  CAS  PubMed  Google Scholar 

  54. Kotak S, Busso C, Gonczy P (2014) NuMA interacts with phosphoinositides and links the mitotic spindle with the plasma membrane. EMBO J 33(16):1815–1830. doi:10.15252/embj.201488147

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Zheng Z, Wan Q, Meixiong G, Du Q (2014) Cell cycle-regulated membrane binding of NuMA contributes to efficient anaphase chromosome separation. Mol Biol Cell 25(5):606–619. doi:10.1091/mbc.E13-08-0474

    Article  PubMed Central  PubMed  Google Scholar 

  56. Kiyomitsu T, Cheeseman IM (2013) Cortical dynein and asymmetric membrane elongation coordinately position the spindle in anaphase. Cell 154(2):391–402. doi:10.1016/j.cell.2013.06.010

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Tepass U, Tanentzapf G, Ward R, Fehon R (2001) Epithelial cell polarity and cell junctions in Drosophila. Annu Rev Genet 35:747–784

    Article  CAS  PubMed  Google Scholar 

  58. Lu B, Roegiers F, Jan LY, Jan YN (2001) Adherens junctions inhibit asymmetric division in the Drosophila epithelium. Nature 409(6819):522–525

    Article  CAS  PubMed  Google Scholar 

  59. McCartney BM, Nathke IS (2008) Cell regulation by the Apc protein Apc as master regulator of epithelia. Curr Opin Cell Biol 20(2):186–193. doi:10.1016/j.ceb.2008.02.001

    Article  CAS  PubMed  Google Scholar 

  60. Lee L, Tirnauer JS, Li J, Schuyler SC, Liu JY, Pellman D (2000) Positioning of the mitotic spindle by a cortical-microtubule capture mechanism. Science 287(5461):2260–2262

    Article  CAS  PubMed  Google Scholar 

  61. Su LK, Burrell M, Hill DE, Gyuris J, Brent R, Wiltshire R, Trent J, Vogelstein B, Kinzler KW (1995) APC binds to the novel protein EB1. Cancer Res 55(14):2972–2977

    CAS  PubMed  Google Scholar 

  62. Green RA, Wollman R, Kaplan KB (2005) APC and EB1 function together in mitosis to regulate spindle dynamics and chromosome alignment. Mol Biol Cell 16(10):4609–4622. doi:10.1091/mbc.E05-03-0259

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Wessels A, Perez-Pomares JM (2004) The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells. Anat Rec A Discov Mol Cell Evol Biol 276(1):43–57. doi:10.1002/ar.a.10129

    Article  CAS  PubMed  Google Scholar 

  64. Zamora M, Manner J, Ruiz-Lozano P (2007) Epicardium-derived progenitor cells require beta-catenin for coronary artery formation. Proc Natl Acad Sci USA 104(46):18109–18114. doi:10.1073/pnas.0702415104

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Hsu YC, Li L, Fuchs E (2014) Emerging interactions between skin stem cells and their niches. Nat Med 20(8):847–856. doi:10.1038/nm.3643

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Kulukian A, Fuchs E (2013) Spindle orientation and epidermal morphogenesis. Philos Trans R Soc Lond B Biol Sci 368(1629):20130016. doi:10.1098/rstb.2013.0016

    Article  PubMed Central  PubMed  Google Scholar 

  67. Tinkle CL, Pasolli HA, Stokes N, Fuchs E (2008) New insights into cadherin function in epidermal sheet formation and maintenance of tissue integrity. Proc Natl Acad Sci USA 105(40):15405–15410. doi:10.1073/pnas.0807374105

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Williams SE, Beronja S, Pasolli HA, Fuchs E (2011) Asymmetric cell divisions promote Notch-dependent epidermal differentiation. Nature 470(7334):353–358. doi:10.1038/nature09793

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Pokutta S, Weis WI (2007) Structure and mechanism of cadherins and catenins in cell-cell contacts. Annu Rev Cell Dev Biol 23:237–261

    Article  CAS  PubMed  Google Scholar 

  70. Nichols SA, Roberts BW, Richter DJ, Fairclough SR, King N (2012) Origin of metazoan cadherin diversity and the antiquity of the classical cadherin/beta-catenin complex. Proc Natl Acad Sci USA 109(32):13046–13051. doi:10.1073/pnas.1120685109

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Inaba M, Yuan H, Salzmann V, Fuller MT, Yamashita YM (2010) E-cadherin is required for centrosome and spindle orientation in Drosophila male germline stem cells. PLoS ONE 5(8):e12473. doi:10.1371/journal.pone.0012473

    Article  PubMed Central  PubMed  Google Scholar 

  72. Zigman M, le Trinh A, Fraser SE, Moens CB (2011) Zebrafish neural tube morphogenesis requires Scribble-dependent oriented cell divisions. Curr Biol 21(1):79–86. doi:10.1016/j.cub.2010.12.005

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. den Elzen N, Buttery CV, Maddugoda MP, Ren G, Yap AS (2009) Cadherin adhesion receptors orient the mitotic spindle during symmetric cell division in mammalian epithelia. Mol Biol Cell 20(16):3740–3750

    Article  Google Scholar 

  74. Mogensen MM, Tucker JB, Mackie JB, Prescott AR, Nathke IS (2002) The adenomatous polyposis coli protein unambiguously localizes to microtubule plus ends and is involved in establishing parallel arrays of microtubule bundles in highly polarized epithelial cells. J Cell Biol 157(6):1041–1048. doi:10.1083/jcb.200203001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Hulsken J, Birchmeier W, Behrens J (1994) E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton. J Cell Biol 127(6 Pt 2):2061–2069

    Article  CAS  PubMed  Google Scholar 

  76. Ebnet K, Suzuki A, Ohno S, Vestweber D (2004) Junctional adhesion molecules (JAMs): More molecules with dual functions? J Cell Sci 117(1):19–29

    Article  CAS  PubMed  Google Scholar 

  77. Severson EA, Lee WY, Capaldo CT, Nusrat A, Parkos CA (2009) Junctional adhesion molecule A interacts with Afadin and PDZ-GEF2 to activate Rap1A, regulate beta1 integrin levels, and enhance cell migration. Mol Biol Cell 20(7):1916–1925

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Iden S, Misselwitz S, Peddibhotla SS, Tuncay H, Rehder D, Gerke V, Robenek H, Suzuki A, Ebnet K (2012) aPKC phosphorylates JAM-A at Ser285 to promote cell contact maturation and tight junction formation. J Cell Biol 196(5):623–639. doi:10.1083/jcb.201104143

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Gliki G, Ebnet K, Aurrand-Lions M, Imhof BA, Adams RH (2004) Spermatid differentiation requires the assembly of a cell polarity complex downstream of junctional adhesion molecule-C. Nature 431(7006):320–324

    Article  CAS  PubMed  Google Scholar 

  80. Scheiermann C, Meda P, Aurrand-Lions M, Madani R, Yiangou Y, Coffey P, Salt TE, Ducrest-Gay D, Caille D, Howell O, Reynolds R, Lobrinus A, Adams RH, Yu AS, Anand P, Imhof BA, Nourshargh S (2007) Expression and function of junctional adhesion molecule-C in myelinated peripheral nerves. Science 318(5855):1472–1475

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Cooke VG, Naik MU, Naik UP (2006) Fibroblast growth factor-2 failed to induce angiogenesis in junctional adhesion molecule-A-deficient mice. Arterioscler Thromb Vasc Biol 26(9):2005–2011

    Article  CAS  PubMed  Google Scholar 

  82. Weber C, Fraemohs L, Dejana E (2007) The role of junctional adhesion molecules in vascular inflammation. Nat Rev Immunol 7(6):467–477

    Article  CAS  PubMed  Google Scholar 

  83. Naik MU, Caplan JL, Naik UP (2014) Junctional adhesion molecule-A suppresses platelet integrin alphaIIbbeta3 signaling by recruiting Csk to the integrin-c-Src complex. Blood 123(9):1393–1402. doi:10.1182/blood-2013-04-496232

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  84. Oceguera-Yanez F, Kimura K, Yasuda S, Higashida C, Kitamura T, Hiraoka Y, Haraguchi T, Narumiya S (2005) Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis. J Cell Biol 168(2):221–232

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  85. Tuncay H, Brinkmann BF, Steinbacher T, Schurmann A, Gerke V, Iden S, Ebnet K (2015) JAM-A regulates cortical dynein localization through Cdc42 to control planar spindle orientation during mitosis. Nat Commun 6:8128. doi:10.1038/ncomms9128

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  86. Jaffe AB, Kaji N, Durgan J, Hall A (2008) Cdc42 controls spindle orientation to position the apical surface during epithelial morphogenesis. The Journal of cell biology 183(4):625–633. doi:10.1083/jcb.200807121

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Jongbloets BC, Pasterkamp RJ (2014) Semaphorin signalling during development. Development 141(17):3292–3297. doi:10.1242/dev.105544

    Article  CAS  PubMed  Google Scholar 

  88. Tamagnone L, Artigiani S, Chen H, He Z, Ming GI, Song H, Chedotal A, Winberg ML, Goodman CS, Poo M, Tessier-Lavigne M, Comoglio PM (1999) Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99(1):71–80

    Article  CAS  PubMed  Google Scholar 

  89. Pascoe HG, Wang Y, Zhang X (2015) Structural mechanisms of plexin signaling. Prog Biophys Mol Biol 118(3):161–168. doi:10.1016/j.pbiomolbio.2015.03.006

    Article  CAS  PubMed  Google Scholar 

  90. Bonventre JV, Yang L (2011) Cellular pathophysiology of ischemic acute kidney injury. J Clin Investig 121(11):4210–4221. doi:10.1172/JCI45161

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. Xia J, Swiercz JM, Banon-Rodriguez I, Matkovic I, Federico G, Sun T, Franz T, Brakebusch CH, Kumanogoh A, Friedel RH, Martin-Belmonte F, Grone HJ, Offermanns S, Worzfeld T (2015) Semaphorin–plexin signalling controls mitotic spindle orientation during epithelial morphogenesis and repair. Dev Cell 33(3):299–313. doi:10.1016/j.devcel.2015.02.001

    Article  CAS  PubMed  Google Scholar 

  92. Lacy DB, Wigelsworth DJ, Scobie HM, Young JA, Collier RJ (2004) Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor. Proc Natl Acad Sci USA 101(17):6367–6372. doi:10.1073/pnas.0401506101

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  93. Liu S, Moayeri M, Leppla SH (2014) Anthrax lethal and edema toxins in anthrax pathogenesis. Trends Microbiol 22(6):317–325. doi:10.1016/j.tim.2014.02.012

    Article  PubMed Central  PubMed  Google Scholar 

  94. Bell SE, Mavila A, Salazar R, Bayless KJ, Kanagala S, Maxwell SA, Davis GE (2001) Differential gene expression during capillary morphogenesis in 3D collagen matrices: regulated expression of genes involved in basement membrane matrix assembly, cell cycle progression, cellular differentiation and G-protein signaling. J Cell Sci 114(Pt 15):2755–2773

    CAS  PubMed  Google Scholar 

  95. Gong Y, Mo C, Fraser SE (2004) Planar cell polarity signalling controls cell division orientation during zebrafish gastrulation. Nature 430(7000):689–693. doi:10.1038/nature02796

    Article  CAS  PubMed  Google Scholar 

  96. Segalen M, Johnston CA, Martin CA, Dumortier JG, Prehoda KE, David NB, Doe CQ, Bellaiche Y (2010) The Fz-Dsh planar cell polarity pathway induces oriented cell division via Mud/NuMA in Drosophila and zebrafish. Dev Cell 19(5):740–752. doi:10.1016/j.devcel.2010.10.004

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  97. Castanon I, Abrami L, Holtzer L, Heisenberg CP, van der Goot FG, Gonzalez-Gaitan M (2013) Anthrax toxin receptor 2a controls mitotic spindle positioning. Nat Cell Biol 15(1):28–39. doi:10.1038/ncb2632

    Article  CAS  PubMed  Google Scholar 

  98. Lai SL, Chan TH, Lin MJ, Huang WP, Lou SW, Lee SJ (2008) Diaphanous-related formin 2 and profilin I are required for gastrulation cell movements. PLoS ONE 3(10):e3439. doi:10.1371/journal.pone.0003439

    Article  PubMed Central  PubMed  Google Scholar 

  99. Kalab P, Heald R (2008) The RanGTP gradient—a GPS for the mitotic spindle. J Cell Sci 121(Pt 10):1577–1586. doi:10.1242/jcs.005959

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank all members of the Institute-associated research group “Cell adhesion and cell polarity” for helpful discussions. We would also like to thank Volker Gerke for continuous support. This work was supported by grants from the Deutsche Forschungsgemeinschaft (EB 160/4-1 and -/4-2) and from the Medical Faculty of the University Münster (IZKF Eb2/028/09 and Eb2/020/14).

Author information

Authors and Affiliations

  1. Institute-Associated Research Group “Cell Adhesion and Cell Polarity”, Institute of Medical Biochemistry, ZMBE, University of Münster, Von-Esmarch-Str. 56, 48149, Muenster, Germany

    Hüseyin Tuncay & Klaus Ebnet

  2. Interdisciplinary Clinical Research Center (IZKF), University of Münster, 48419, Muenster, Germany

    Klaus Ebnet

Authors
  1. Hüseyin Tuncay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Klaus Ebnet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Klaus Ebnet.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tuncay, H., Ebnet, K. Cell adhesion molecule control of planar spindle orientation. Cell. Mol. Life Sci. 73, 1195–1207 (2016). https://doi.org/10.1007/s00018-015-2116-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-015-2116-7

Keywords

Search

Navigation