Front-signal-dependent accumulation of the RHOA inhibitor FAM65B at leading edges polarizes neutrophils.

Article Details

Citation

Gao K, Tang W, Li Y, Zhang P, Wang D, Yu L, Wang C, Wu D

Front-signal-dependent accumulation of the RHOA inhibitor FAM65B at leading edges polarizes neutrophils.

J Cell Sci. 2015 Mar 1;128(5):992-1000. doi: 10.1242/jcs.161497. Epub 2015 Jan 14.

PubMed ID
25588844 [ View in PubMed
]
Abstract

A hallmark of neutrophil polarization is the back localization of active RHOA and phosphorylated myosin light chain (pMLC, also known as MYL2). However, the mechanism for the polarization is not entirely clear. Here, we show that FAM65B, a newly identified RHOA inhibitor, is important for the polarization. When FAM65B is phosphorylated, it binds to 14-3-3 family proteins and becomes more stable. In neutrophils, chemoattractants stimulate FAM65B phosphorylation largely depending on the signals from the front of the cells that include those mediated by phospholipase Cbeta (PLCbeta) and phosphoinositide 3-kinase gamma (PI3Kgamma), leading to FAM65B accumulation at the leading edge. Concordantly, FAM65B deficiency in neutrophils resulted in an increase in RHOA activity and localization of pMLC to the front of cells, as well as defects in chemotaxis directionality and adhesion to endothelial cells under flow. These data together elucidate a mechanism for RHOA and pMLC polarization in stimulated neutrophils through direct inhibition of RHOA by FAM65B at the leading edge.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
14-3-3 protein beta/alphaP31946Details
14-3-3 protein thetaP27348Details