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

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