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© Research
Publication : Molecular and cellular biology

Coronin1 proteins dictate rac1 intracellular dynamics and cytoskeletal output

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Molecular and cellular biology - 30 Jun 2014

Ojeda V, Castro-Castro A, Bustelo XR

Link to Pubmed [PMID] – 24980436

Mol. Cell. Biol. 2014 Sep;34(18):3388-406

Rac1 regulates lamellipodium formation, myosin II-dependent contractility, and focal adhesions during cell migration. While the spatiotemporal assembly of those processes is well characterized, the signaling mechanisms involved remain obscure. We report here that the cytoskeleton-related Coronin1A and -1B proteins control a myosin II inactivation-dependent step that dictates the intracellular dynamics and cytoskeletal output of active Rac1. This step is signaling-branch specific, since it affects the functional competence of active Rac1 only when forming complexes with downstream ArhGEF7 and Pak proteins in actomyosin-rich structures. The pathway is used by default unless Rac1 is actively rerouted away from the structures by upstream activators and signals from other Rho GTPases. These results indicate that Coronin1 proteins are at the center of a regulatory hub that coordinates Rac1 activation, effector exchange, and the F-actin organization state during cell signaling. Targeting this route could be useful to hamper migration of cancer cells harboring oncogenic RAC1 mutations.

http://www.ncbi.nlm.nih.gov/pubmed/24980436