Novel Coronin7 interactions with Cdc42 and N-WASP regulate actin organization and Golgi morphology
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2016-05Author
Bhattacharya, K.Swaminathan, Karthic
Peche, V.S.
Clemen, C.S.
Knyphausen, P.
Lammers, M.
Noegel, A.A.
Rastetter, R.H.
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The contribution of the actin cytoskeleton to the unique architecture of the Golgi complex is manifold. An important player in this process is Coronin7 (CRN7), a Golgi-resident protein that stabilizes F-actin assembly at the trans-Golgi network (TGN) thereby facilitating anterograde trafficking. Here, we establish that CRN7-mediated association of F-actin with the Golgi apparatus is distinctly modulated via the small Rho GTPase Cdc42 and N-WASP. We identify N-WASP as a novel interaction partner of CRN7 and demonstrate that CRN7 restricts spurious F-actin reorganizations by repressing N-WASP ‘hyperactivity’ upon constitutive Cdc42 activation. Loss of CRN7 leads to increased cellular F-actin content and causes a concomitant disruption of the Golgi structure. CRN7 harbours a Cdc42- and Rac-interactive binding (CRIB) motif in its tandem β-propellers and binds selectively to GDP-bound Cdc42N17 mutant. We speculate that CRN7 can act as a cofactor for active Cdc42 generation. Mutation of CRIB motif residues that abrogate Cdc42 binding to CRN7 also fail to rescue the cellular defects in fibroblasts derived from CRN7 KO mice. Cdc42N17 overexpression partially rescued the KO phenotypes whereas N-WASP overexpression failed to do so. We conclude that CRN7 spatiotemporally influences F-actin organization and Golgi integrity in a Cdc42- and N-WASP-dependent manner.Version
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Bhattacharya K, Swaminathan K, Peche VS et al (2016) Novel Coronin7 interactions with Cdc42 and N-WASP regulate actin organization and Golgi morphology. Scientific Reports. 6: Article number: 25411.Link to Version of Record
https://doi.org/10.1038/srep25411Type
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.1038/srep25411