GPCR-mediated PLC??/PKC?/PKD signaling pathway regulates the cofilin phosphatase slingshot 2 in neutrophil chemotaxis.

ABSTRACT: Chemotaxis requires precisely coordinated polymerization and depolymerization of the actin cytoskeleton at leading fronts of migrating cells. However, GPCR activation-controlled F-actin depolymerization remains largely elusive. Here, we reveal a novel signaling pathway, including G?i, PLC, PKC?, protein kinase D (PKD), and SSH2, in control of cofilin phosphorylation and actin cytoskeletal reorganization, which is essential for neutrophil chemotaxis. We show that PKD is essential for neutrophil chemotaxis and that GPCR-mediated PKD activation depends on PLC/PKC signaling. More importantly, we discover that GPCR activation recruits/activates PLC?2 in a PI3K-dependent manner. We further verify that PKC? specifically interacts with PKD1 and is required for chemotaxis. Finally, we identify slingshot 2 (SSH2), a phosphatase of cofilin (actin depolymerization factor), as a target of PKD1 that regulates cofilin phosphorylation and remodeling of the actin cytoskeleton during neutrophil chemotaxis.

SUBMITTER: Xu X 

PROVIDER: S-EPMC4342024 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature