title: Novel Coronin7 interactions with Cdc42 and N-WASP regulate actin organization and Golgi morphology.
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 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.
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, 50931 Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.
authors.forename: Kurchi
authors.initials: K
authors.lastname: Bhattacharya
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, 50931 Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.
authors.forename: Karthic
authors.initials: K
authors.lastname: Swaminathan
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, 50931 Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.
authors.forename: Vivek S
authors.initials: VS
authors.lastname: Peche
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, 50931 Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.
authors.forename: Christoph S
authors.initials: CS
authors.lastname: Clemen
authors.affiliation: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Knyphausen
authors.affiliation: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lammers
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, 50931 Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.
authors.forename: Angelika A
authors.initials: AA
authors.lastname: Noegel
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, 50931 Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.
authors.forename: Raphael H
authors.initials: RH
authors.lastname: Rastetter
mesh_terms: D000199:Actins / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D005347:Fibroblasts; D017353:Gene Deletion; D018390:Gene Targeting; D056426:Genetic Loci; D006056:Golgi Apparatus / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D008840:Microfilament Proteins; D051316:Wiskott-Aldrich Syndrome Protein; C072061:coronin proteins; D006153:Guanosine Diphosphate; D020764:cdc42 GTP-Binding Protein