RGD Reference Report - Chronophin coordinates cell leading edge dynamics by controlling active cofilin levels. - Rat Genome Database

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Chronophin coordinates cell leading edge dynamics by controlling active cofilin levels.

Authors: Delorme-Walker, V  Seo, JY  Gohla, A  Fowler, B  Bohl, B  DerMardirossian, C 
Citation: Delorme-Walker V, etal., Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):E5150-9. doi: 10.1073/pnas.1510945112. Epub 2015 Aug 31.
RGD ID: 11568705
Pubmed: (View Article at PubMed) PMID:26324884
DOI: Full-text: DOI:10.1073/pnas.1510945112

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.

Gene Ontology Annotations    

Biological Process

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Cfl1  (cofilin 1)

Additional Information