title: A Cdc42- and Rac-interactive binding (CRIB) domain mediates functions of coronin.
abstract: The Cdc42- and Rac-interactive binding motif (CRIB) of coronin binds to Rho GTPases with a preference for GDP-loaded Rac. Mutation of the Cdc42- and Rac-interactive binding motif abrogates Rac binding. This results in increased 1evels of activated Rac in coronin-deficient Dictyostelium cells (corA(-)), which impacts myosin II assembly. corA(-) cells show increased accumulation of myosin II in the cortex of growth-phase cells. Myosin II assembly is regulated by myosin heavy chain kinase-mediated phosphorylation of its tail. Kinase activity depends on the activation state of the p21-activated kinase a. The myosin II defect of corA(-) mutant is alleviated by dominant-negative p21-activated kinase a. It is rescued by wild-type coronin, whereas coronin carrying a mutated Cdc42- and Rac-interactive binding motif failed to rescue the myosin defect in corA(-) mutant cells. Ectopically expressed myosin heavy chain kinases affinity purified from corA(-) cells show reduced kinase activity. We propose that coronin through its affinity for GDP-Rac regulates the availability of GTP-Rac for activation of downstream effectors.
authors.affiliation: Center for Biochemistry, Medical Faculty, Center for Molecular Medicine Cologne and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Köln, Germany.
authors.forename: Karthic
authors.initials: K
authors.lastname: Swaminathan
authors.forename: Annette
authors.initials: A
authors.lastname: Müller-Taubenberger
authors.forename: Jan
authors.initials: J
authors.lastname: Faix
authors.forename: Francisco
authors.initials: F
authors.lastname: Rivero
authors.forename: Angelika A
authors.initials: AA
authors.lastname: Noegel
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004023:Dictyostelium / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000378:metabolism; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D054378:Acetogenins
chemical_list: D015107:4-Butyrolactone; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D015800:Protozoan Proteins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; C438920:coronin acetogenin; D054378:Acetogenins; C033142:myosin-heavy-chain kinase
keywords: Rac GTPases; cell signaling; cytoskeleton; protein–protein interaction