M-cadherin Activates Rac1 GTPase Through the Rho-GEF Trio During Myoblast Fusion

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2007 Mar 3

PMID 17332503

Citations 73

Authors

Sophie Charrasse

Franck Comunale

Mathieu Fortier

Elodie Portales-Casamar

Anne Debant

Cecile Gauthier-Rouviere

Affiliations

Soon will be listed here.

Abstract

Cadherins are transmembrane glycoproteins that mediate Ca(2+)-dependent homophilic cell-cell adhesion and play crucial role during skeletal myogenesis. M-cadherin is required for myoblast fusion into myotubes, but its mechanisms of action remain unknown. The goal of this study was to cast some light on the nature of the M-cadherin-mediated signals involved in myoblast fusion into myotubes. We found that the Rac1 GTPase activity is increased at the time of myoblast fusion and it is required for this process. Moreover, we showed that M-cadherin-dependent adhesion activates Rac1 and demonstrated the formation of a multiproteic complex containing M-cadherin, the Rho-GEF Trio, and Rac1 at the onset of myoblast fusion. Interestingly, Trio knockdown efficiently blocked both the increase in Rac1-GTP levels, observed after M-cadherin-dependent contact formation, and myoblast fusion. We conclude that M-cadherin-dependent adhesion can activate Rac1 via the Rho-GEF Trio at the time of myoblast fusion.

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References

Hollnagel A, Grund C, Franke W, Arnold H . The cell adhesion molecule M-cadherin is not essential for muscle development and regeneration. Mol Cell Biol. 2002; 22(13):4760-70. PMC: 133893. DOI: 10.1128/MCB.22.13.4760-4770.2002. View

Ridley A, Hall A . Distinct patterns of actin organization regulated by the small GTP-binding proteins Rac and Rho. Cold Spring Harb Symp Quant Biol. 1992; 57:661-71. DOI: 10.1101/sqb.1992.057.01.072. View

Kang J, Feinleib J, Knox S, Ketteringham M, Krauss R . Promyogenic members of the Ig and cadherin families associate to positively regulate differentiation. Proc Natl Acad Sci U S A. 2003; 100(7):3989-94. PMC: 153035. DOI: 10.1073/pnas.0736565100. View

Katoh H, Negishi M . RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. Nature. 2003; 424(6947):461-4. DOI: 10.1038/nature01817. View

Chen E, Pryce B, Tzeng J, Gonzalez G, Olson E . Control of myoblast fusion by a guanine nucleotide exchange factor, loner, and its effector ARF6. Cell. 2003; 114(6):751-62. DOI: 10.1016/s0092-8674(03)00720-7. View

Wheelock M, Johnson K . Cadherin-mediated cellular signaling. Curr Opin Cell Biol. 2003; 15(5):509-14. DOI: 10.1016/s0955-0674(03)00101-7. View

Wheelock M, Johnson K . Cadherins as modulators of cellular phenotype. Annu Rev Cell Dev Biol. 2003; 19:207-35. DOI: 10.1146/annurev.cellbio.19.011102.111135. View

Musa H, Orton C, Morrison E, Peckham M . Microtubule assembly in cultured myoblasts and myotubes following nocodazole induced microtubule depolymerisation. J Muscle Res Cell Motil. 2003; 24(4-6):301-8. PMC: 1351055. View

Charrasse S, Causeret M, Comunale F, Bonet-Kerrache A, Gauthier-Rouviere C . Rho GTPases and cadherin-based cell adhesion in skeletal muscle development. J Muscle Res Cell Motil. 2003; 24(4-6):309-13. View

10.

Pouliot Y, Gravel M, Holland P . Developmental regulation of M-cadherin in the terminal differentiation of skeletal myoblasts. Dev Dyn. 1994; 200(4):305-12. DOI: 10.1002/aja.1002000405. View

11.

Rose O, Rohwedel J, Reinhardt S, Bachmann M, Cramer M, Rotter M . Expression of M-cadherin protein in myogenic cells during prenatal mouse development and differentiation of embryonic stem cells in culture. Dev Dyn. 1994; 201(3):245-59. DOI: 10.1002/aja.1002010308. View

12.

Cifuentes-Diaz C, Nicolet M, Alameddine H, Goudou D, Dehaupas M, Rieger F . M-cadherin localization in developing adult and regenerating mouse skeletal muscle: possible involvement in secondary myogenesis. Mech Dev. 1995; 50(1):85-97. DOI: 10.1016/0925-4773(94)00327-j. View

13.

Zeschnigk M, Kozian D, Kuch C, Schmoll M, Starzinski-Powitz A . Involvement of M-cadherin in terminal differentiation of skeletal muscle cells. J Cell Sci. 1995; 108 ( Pt 9):2973-81. DOI: 10.1242/jcs.108.9.2973. View

14.

Debant A, Serra-Pages C, Seipel K, OBrien S, Tang M, Park S . The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains. Proc Natl Acad Sci U S A. 1996; 93(11):5466-71. PMC: 39269. DOI: 10.1073/pnas.93.11.5466. View

15.

Cifuentes-Diaz C, Goudou D, Padilla F, Facchinetti P, Nicolet M, Mege R . M-cadherin distribution in the mouse adult neuromuscular system suggests a role in muscle innervation. Eur J Neurosci. 1996; 8(8):1666-76. DOI: 10.1111/j.1460-9568.1996.tb01310.x. View

16.

Bahjaoui-Bouhaddi M, Padilla F, Nicolet M, Cifuentes-Diaz C, Fellmann D, Mege R . Localized deposition of M-cadherin in the glomeruli of the granular layer during the postnatal development of mouse cerebellum. J Comp Neurol. 1997; 378(2):180-95. View

17.

Doberstein S, Fetter R, Mehta A, Goodman C . Genetic analysis of myoblast fusion: blown fuse is required for progression beyond the prefusion complex. J Cell Biol. 1997; 136(6):1249-61. PMC: 2132517. DOI: 10.1083/jcb.136.6.1249. View

18.

Kuch C, Winnekendonk D, Butz S, Unvericht U, Kemler R, Starzinski-Powitz A . M-cadherin-mediated cell adhesion and complex formation with the catenins in myogenic mouse cells. Exp Cell Res. 1997; 232(2):331-8. DOI: 10.1006/excr.1997.3519. View

19.

Simons K, Ikonen E . Functional rafts in cell membranes. Nature. 1997; 387(6633):569-72. DOI: 10.1038/42408. View

20.

Erickson M, Galletta B, Abmayr S . Drosophila myoblast city encodes a conserved protein that is essential for myoblast fusion, dorsal closure, and cytoskeletal organization. J Cell Biol. 1997; 138(3):589-603. PMC: 2141626. DOI: 10.1083/jcb.138.3.589. View