Universität zu Köln

Bhattacharya, Kurchi, Swaminathan, Karthic ORCID: 0000-0002-0981-7549, Peche, Vivek S., Clemen, Christoph S., Knyphausen, Philipp, Lammers, Michael ORCID: 0000-0003-4168-4640, Noegel, Angelika A. and Rastetter, Raphael H. (2016). Novel Coronin7 interactions with Cdc42 and N-WASP regulate actin organization and Golgi morphology. Sci Rep, 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

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 beta-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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bhattacharya, Kurchi UNSPECIFIED UNSPECIFIED UNSPECIFIED Swaminathan, Karthic UNSPECIFIED orcid.org/0000-0002-0981-7549 UNSPECIFIED Peche, Vivek S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Clemen, Christoph S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Knyphausen, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Lammers, Michael UNSPECIFIED orcid.org/0000-0003-4168-4640 UNSPECIFIED Noegel, Angelika A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rastetter, Raphael H. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-275969
DOI:	10.1038/srep25411
Journal or Publication Title:	Sci Rep
Volume:	6
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GUANINE-NUCLEOTIDE-EXCHANGE; ALDRICH SYNDROME PROTEIN; GTPASE-BINDING DOMAIN; CELL POLARITY; LIVING CELLS; CRIB DOMAIN; RHO GTPASES; E3 LIGASE; COMPLEX; APPARATUS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27596