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A Cdc42- and Rac-interactive binding (CRIB) domain mediates functions of coronin

Author:
Swaminathan, Karthic, Müller-Taubenberger, Annette, Faix, Jan, Rivero, Francisco, Noegel, Angelika A.
Source:
Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.1 pp. E25
ISSN:
0027-8424
Subject:
Dictyostelium, cortex, guanosinetriphosphatase, mutants, mutation, myosin heavy chains, phosphorylation, phosphotransferases (kinases)
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.
Agid:
1785912