p120-catenin binding masks an endocytic signal conserved in classical cadherinsReportar como inadecuado

p120-catenin binding masks an endocytic signal conserved in classical cadherins - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal Title:

Journal of Cell Biology


Volume 199, Number 2


Rockefeller University Press | 2012-10-15, Pages 365-380

Type of Work:

Article | Final Publisher PDF

Abstract: p120-catenin p120 binds to the cytoplasmic tails of classical cadherins and inhibits cadherin endocytosis. Although p120 regulation of cadherin internalization is thought to be important for adhesive junction dynamics, the mechanism by which p120 modulates cadherin endocytosis is unknown. In this paper, we identify a dual-function motif in classical cadherins consisting of three highly conserved acidic residues that alternately serve as a p120-binding interface and an endocytic signal. Mutation of this motif resulted in a cadherin variant that was both p120 uncoupled and resistant to endocytosis. In endothelial cells, in which dynamic changes in adhesion are important components of angiogenesis and inflammation, a vascular endothelial cadherin VE-cadherin mutant defective in endocytosis assembled normally into cell–cell junctions but potently suppressed cell migration in response to vascular endothelial growth factor. These results reveal the mechanistic basis by which p120 stabilizes cadherins and demonstrate that VE-cadherin endocytosis is crucial for endothelial cell migration in response to an angiogenic growth factor.

Subject: Biology, Cell - Research Funding: This work was supported by grants from the National Institutes of Health R01AR050501 and R01AR048266 to A.P. Kowalczyk, the Integrated Cellular Imaging Microscopy Core of the Emory Neuroscience National Institute of Neurological Disorders and Stroke Core Facilities grant P30NS055077, and the Canadian Cancer Society to M. Ikura. B.A. Nanes was supported by fellowships from the American Heart Association and the National Institutes of Health F30HL110447.

Autor: Benjamin A. Nanes, Christine Chiasson-MacKenzie, Anthony M. Lowery, Noboru Ishiyama, Victor Faundez, Mitsuhiko Ikura, Peter A. Vi

Fuente: https://open.library.emory.edu/


Documentos relacionados