A lateral belt of cortical LGN and NuMA guides mitotic spindle movements and planar division in neuroepithelial cells

[en] To maintain tissue architecture, epithelial cells divide in a planar fashion, perpendicular to their main polarity axis. As the centrosome resumes an apical localization in interphase, planar spindle orientation is reset at each cell cycle. We used three-dimensional live imaging of GFP-labeled centrosomes to investigate the dynamics of spindle orientation in chick neuroepithelial cells. The mitotic spindle displays stereotypic movements during metaphase, with an active phase of planar orientation and a subsequent phase of planar maintenance before anaphase. We describe the localization of the NuMA and LGN proteins in a belt at the lateral cell cortex during spindle orientation. Finally, we show that the complex formed of LGN, NuMA, and of cortically located Gai subunits is necessary for spindle movements and regulates the dynamics of spindle orientation. The restricted localization of LGN and NuMA in the lateral belt is instructive for the planar alignment of the mitotic spindle, and required for its planar maintenance

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Peyre, Elise ; Université de Liège - ULiège > Giga - Neurosciences

Jaouen, Florence; Université de la Méditerranée/Aix-Marseille II > Developmental Biology Institute (IBDML) > CNRS UMR6216

Saadaoui, Mehdi; Université de la Méditerranée/Aix-Marseille II > Developmental Biology Institute (IBDML) > CNRS UMR6216

Haren, Laurence; CNRS-Pierre Fabre

Merdes, Andreas; CNRS-Pierre Fabre

Durbec, Pascale; Université de la Méditerranée/Aix-Marseille II, > Developmental Biology Institute (IBDML) > CNRS UMR6216

Morin, Xavier; Ecole Normale Supérieure, Institut de Biologie de l’ENS, IBENS > INSERM, U1024 ; CNRS, UMR 8197

Language :

English

Title :

A lateral belt of cortical LGN and NuMA guides mitotic spindle movements and planar division in neuroepithelial cells

Publication date :

28 March 2011

Journal title :

Journal of Cell Biology

ISSN :

0021-9525

eISSN :

1540-8140

Publisher :

Rockefeller University Press, New York, United States - New York

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 05 January 2015

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118

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109

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122

Bibliography

Aaku-Saraste, E., B. Oback, A. Hellwig, and W.B. Huttner. 1997. Neuroepithelial cells downregulate their plasma membrane polarity prior to neural tube closure and neurogenesis. Mech. Dev. 69:71-81. doi:10.1016/S0925-4773(97)00156-1.
Adams, R.J. 1996. Metaphase spindles rotate in the neuroepithelium of rat cerebral cortex. J. Neurosci. 16:7610-7618.
Baena-López, L.A., A. Baonza, and A. García-Bellido. 2005. The orientation of cell divisions determines the shape of Drosophila organs. Curr. Biol. 15:1640-1644. doi:10.1016/j.cub.2005.07.062.
Barnes, A.P., B.N. Lilley, Y.A. Pan, L.J. Plummer, A.W. Powell, A.N. Raines, J.R. Sanes, and F. Polleux. 2007. LKB1 and SAD kinases define a pathway required for the polarization of cortical neurons. Cell. 129:549-563. doi:10.1016/j.cell.2007.03.025.
Bellaiche, Y., and M. Gotta. 2005. Heterotrimeric G proteins and regulation of size asymmetry during cell division. Curr. Opin. Cell Biol. 17:658-663. doi:10.1016/j.ceb.2005.10.002.
Blumer, J.B., M.L. Bernard, Y.K. Peterson, J. Nezu, P. Chung, D.J. Dunican, J.A. Knoblich, and S.M. Lanier. 2003. Interaction of activator of G-protein signaling 3 (AGS3) with LKB1, a serine/threonine kinase involved in cell polarity and cell cycle progression: phosphorylation of the G-protein regulatory (GPR) motif as a regulatory mechanism for the interaction of GPR motifs with Gi alpha. J. Biol. Chem. 278:23217-23220. doi:10.1074/jbc.C200686200.
Boehlke, C., F. Kotsis, V. Patel, S. Braeg, H. Voelker, S. Bredt, T. Beyer, H. Janusch, C. Hamann, M. Gödel, et al. 2010. Primary cilia regulate mTORC1 activity and cell size through Lkb1. Nat. Cell Biol. 12:1115-1122. doi:10.1038/ncb2117.
Busson, S., D. Dujardin, A. Moreau, J. Dompierre, and J.R. De Mey. 1998. Dynein and dynactin are localized to astral microtubules and at cortical sites in mitotic epithelial cells. Curr. Biol. 8:541-544. doi:10.1016/S0960-9822(98)70208-8.
Cabernard, C., and C.Q. Doe. 2009. Apical/basal spindle orientation is required for neuroblast homeostasis and neuronal differentiation in Drosophila. Dev. Cell. 17:134-141. doi:10.1016/j.devcel.2009.06.009.
Costa, M.R., G. Wen, A. Lepier, T. Schroeder, and M. Götz. 2008. Par-complex proteins promote proliferative progenitor divisions in the developing mouse cerebral cortex. Development. 135:11-22. doi:10.1242/dev.009951.
Du, Q., and I.G. Macara. 2004. Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell. 119:503-516. doi:10.1016/j.cell.2004.10.028.
Du, Q., P.T. Stukenberg, and I.G. Macara. 2001. A mammalian Partner of inscuteable binds NuMA and regulates mitotic spindle organization. Nat. Cell Biol. 3:1069-1075. doi:10.1038/ncb1201-1069.
Du, Q., L. Taylor, D.A. Compton, and I.G. Macara. 2002. LGN blocks the ability of NuMA to bind and stabilize microtubules. A mechanism for mitotic spindle assembly regulation. Curr. Biol. 12:1928-1933. doi:10.1016/S0960-9822(02)01298-8.
Fischer, E., E. Legue, A. Doyen, F. Nato, J.F. Nicolas, V. Torres, M. Yaniv, and M. Pontoglio. 2006. Defective planar cell polarity in polycystic kidney disease. Nat. Genet. 38:21-23. doi:10.1038/ng1701.
Fleming, E.S., M. Zajac, D.M. Moschenross, D.C. Montrose, D.W. Rosenberg, A.E. Cowan, and J.S. Tirnauer. 2007. Planar spindle orientation and asymmetric cytokinesis in the mouse small intestine. J. Histochem. Cytochem. 55:1173-1180. doi:10.1369/jhc.7A7234.2007.
Fleming, E.S., M. Temchin, Q. Wu, L. Maggio-Price, and J.S. Tirnauer. 2009. Spindle misorientation in tumors from APC(min/+) mice. Mol. Carcinog. 48:592-598. doi:10.1002/mc.20506.
Gönczy, P. 2008. Mechanisms of asymmetric cell division: flies and worms pave the way. Nat. Rev. Mol. Cell Biol. 9:355-366. doi:10.1038/nrm2388.
Hao, Y., Q. Du, X. Chen, Z. Zheng, J.L. Balsbaugh, S. Maitra, J. Shabanowitz, D.F. Hunt, and I.G. Macara. 2010. Par3 controls epithelial spindle orientation by aPKC-mediated phosphorylation of apical Pins. Curr. Biol. 20:1809-1818. doi:10.1016/j.cub.2010.09.032.
Haydar, T.F., E. Ang Jr., and P. Rakic. 2003. Mitotic spindle rotation and mode of cell division in the developing telencephalon. Proc. Natl. Acad. Sci. USA. 100:2890-2895. doi:10.1073/pnas.0437969100.
Jaffe, A.B., N. Kaji, J. Durgan, and A. Hall. 2008. Cdc42 controls spindle orientation to position the apical surface during epithelial morphogenesis. J. Cell Biol. 183:625-633. doi:10.1083/jcb.200807121.
Konno, D., G. Shioi, A. Shitamukai, A. Mori, H. Kiyonari, T. Miyata, and F. Matsuzaki. 2008. Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat. Cell Biol. 10:93-101. doi:10.1038/ncb1673.
Kosodo, Y., K. Röper, W. Haubensak, A.M. Marzesco, D. Corbeil, and W.B. Huttner. 2004. Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells. EMBO J. 23:2314-2324. doi:10.1038/sj.emboj.7600223.
Merdes, A., K. Ramyar, J.D. Vechio, and D.W. Cleveland. 1996. A complex of NuMA and cytoplasmic dynein is essential for mitotic spindle assembly. Cell. 87:447-458. doi:10.1016/S0092-8674(00)81365-3.
Merdes, A., R. Heald, K. Samejima, W.C. Earnshaw, and D.W. Cleveland. 2000. Formation of spindle poles by dynein/dynactin-dependent transport of NuMA. J. Cell Biol. 149:851-862. doi:10.1083/jcb.149.4.851.
Morin, X., F. Jaouen, and P. Durbec. 2007. Control of planar divisions by the G-protein regulator LGN maintains progenitors in the chick neuroepithelium. Nat. Neurosci. 10:1440-1448. doi:10.1038/nn1984.
Nguyen-Ngoc, T., K. Afshar, and P. Gönczy. 2007. Coupling of cortical dynein and G alpha proteins mediates spindle positioning in Caenorhabditis elegans. Nat. Cell Biol. 9:1294-1302. doi:10.1038/ncb1649.
Noctor, S.C., V. Martínez-Cerdeño, and A.R. Kriegstein. 2008. Distinct behaviors of neural stem and progenitor cells underlie cortical neurogenesis. J. Comp. Neurol. 508:28-44. doi:10.1002/cne.21669.
Poulson, N.D., and T. Lechler. 2010. Robust control of mitotic spindle orientation in the developing epidermis. J. Cell Biol. 191:915-922. doi:10.1083/jcb.201008001.
Rebollo, E., P. Sampaio, J. Januschke, S. Llamazares, H. Varmark, and C. González. 2007. Functionally unequal centrosomes drive spindle orientation in asymmetrically dividing Drosophila neural stem cells. Dev. Cell. 12:467-474. doi:10.1016/j.devcel.2007.01.021.
Rebollo, E., M. Roldán, and C. Gonzalez. 2009. Spindle alignment is achieved without rotation after the first cell cycle in Drosophila embryonic neuroblasts. Development. 136:3393-3397. doi:10.1242/dev.041822.
Reinsch, S., and E. Karsenti. 1994. Orientation of spindle axis and distribution of plasma membrane proteins during cell division in polarized MDCKII cells. J. Cell Biol. 126:1509-1526. doi:10.1083/jcb.126.6.1509.
Roszko, I., C. Afonso, D. Henrique, and L. Mathis. 2006. Key role played by RhoA in the balance between planar and apico-basal cell divisions in the chick neuroepithelium. Dev. Biol. 298:212-224. doi:10.1016/j.ydbio.2006.06.031.
Rusan, N.M., and M. Peifer. 2007. A role for a novel centrosome cycle in asymmetric cell division. J. Cell Biol. 177:13-20. doi:10.1083/jcb.200612140.
Sanada, K., and L.H. Tsai. 2005. G protein betagamma subunits and AGS3 control spindle orientation and asymmetric cell fate of cerebral cortical progenitors. Cell. 122:119-131. doi:10.1016/j.cell.2005.05.009.
Sans, N., P.Y. Wang, Q. Du, R.S. Petralia, Y.X. Wang, S. Nakka, J.B. Blumer, I.G. Macara, and R.J. Wenthold. 2005. mPins modulates PSD-95 and SAP102 trafficking and influences NMDA receptor surface expression. Nat. Cell Biol. 7:1179-1190. doi:10.1038/ncb1325.
Schaefer, M., M. Petronczki, D. Dorner, M. Forte, and J.A. Knoblich. 2001. Heterotrimeric G proteins direct two modes of asymmetric cell division in the Drosophila nervous system. Cell. 107:183-194. doi:10.1016/S0092-8674(01)00521-9.
Sebbagh, M., M.J. Santoni, B. Hall, J.P. Borg, and M.A. Schwartz. 2009. Regulation of LKB1/STRAD localization and function by E-cadherin. Curr. Biol. 19:37-42. doi:10.1016/j.cub.2008.11.033.
Shioi, G., D. Konno, A. Shitamukai, and F. Matsuzaki. 2009. Structural basis for self-renewal of neural progenitors in cortical neurogenesis. Cereb. Cortex. 19(Suppl 1):i55-i61. doi:10.1093/cercor/bhp042
Siderovski, D.P., M. Diversé-Pierluissi, and L. De Vries. 1999. The GoLoco motif: a Galphai/o binding motif and potential guanine-nucleotide exchange factor. Trends Biochem. Sci. 24:340-341. doi:10.1016/S0968-0004(99)01441-3.
Siller, K.H., and C.Q. Doe. 2008. Lis1/dynactin regulates metaphase spindle orientation in Drosophila neuroblasts. Dev. Biol. 319:1-9. doi:10.1016/j.ydbio.2008.03.018.
Théry, M., A. Jiménez-Dalmaroni, V. Racine, M. Bornens, and F. Jülicher. 2007. Experimental and theoretical study of mitotic spindle orientation. Nature. 447:493-496. doi:10.1038/nature05786.
Willard, F.S., R.J. Kimple, and D.P. Siderovski. 2004. Return of the GDI: the GoLoco motif in cell division. Annu. Rev. Biochem. 73:925-951. doi:10.1146/annurev.biochem.73.011303.073756.
Woodard, G.E., N.N. Huang, H. Cho, T. Miki, G.G. Tall, and J.H. Kehrl. 2010. Ric-8A and Gi alpha recruit LGN, NuMA, and dynein to the cell cortex to help orient the mitotic spindle. Mol. Cell. Biol. 30:3519-3530. doi:10.1128/MCB.00394-10.
Yamashita, Y.M., and M.T. Fuller. 2008. Asymmetric centrosome behavior and the mechanisms of stem cell division. J. Cell Biol. 180:261-266. doi:10.1083/jcb.200707083.
Yingling, J., Y.H. Youn, D. Darling, K. Toyo-Oka, T. Pramparo, S. Hirotsune, and A. Wynshaw-Boris. 2008. Neuroepithelial stem cell proliferation requires LIS1 for precise spindle orientation and symmetric division. Cell. 132:474-486. doi:10.1016/j.cell.2008.01.026.
Yu, F., X. Morin, Y. Cai, X. Yang, and W. Chia. 2000. Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in inscuteable apical localization. Cell. 100:399-409. doi:10.1016/S0092-8674(00)80676-5.
Yu, F., C.T. Ong, W. Chia, and X. Yang. 2002. Membrane targeting and asymmetric localization of Drosophila partner of inscuteable are discrete steps controlled by distinct regions of the protein. Mol. Cell. Biol. 22:4230-4240. doi:10.1128/MCB.22.12.4230-4240.2002.
Zheng, Z., H. Zhu, Q. Wan, J. Liu, Z. Xiao, D.P. Siderovski, and Q. Du. 2010. LGN regulates mitotic spindle orientation during epithelial morphogenesis. J. Cell Biol. 189:275-288. doi:10.1083/jcb.200910021.