Chronophin coordinates cell leading edge dynamics by controlling active cofilin levels

Proceedings of the National Academy of Sciences of the United States of America
Violaine Delorme-WalkerCéline DerMardirossian

Abstract

Cofilin, a critical player of actin dynamics, is spatially and temporally regulated to control the direction and force of membrane extension required for cell locomotion. In carcinoma cells, although the signaling pathways regulating cofilin activity to control cell direction have been established, the molecular machinery required to generate the force of the protrusion remains unclear. We show that the cofilin phosphatase chronophin (CIN) spatiotemporally regulates cofilin activity at the cell edge to generate persistent membrane extension. We show that CIN translocates to the leading edge in a PI3-kinase-, Rac1-, and cofilin-dependent manner after EGF stimulation to activate cofilin, promotes actin free barbed end formation, accelerates actin turnover, and enhances membrane protrusion. In addition, we establish that CIN is crucial for the balance of protrusion/retraction events during cell migration. Thus, CIN coordinates the leading edge dynamics by controlling active cofilin levels to promote MTLn3 cell protrusion.

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Citations

Feb 14, 2016·Cytoskeleton·James R Bamburg, Barbara W Bernstein
Apr 2, 2019·Cancer Biomarkers : Section a of Disease Markers·Yujing QinZhijia Zhan
Feb 23, 2021·Frontiers in Cell and Developmental Biology·Jing XuHuangan Wu

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