4.8 Article

The GTPase-Activating Protein RN-tre Controls Focal Adhesion Turnover and Cell Migration

期刊

CURRENT BIOLOGY
卷 23, 期 23, 页码 2355-2364

出版社

CELL PRESS
DOI: 10.1016/j.cub.2013.09.060

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资金

  1. Associazione Italiana per la Ricerca sul Cancro [6310]
  2. European Community
  3. European Research Council
  4. Italian Ministries of Education, Universities, and Research (MIUR) and Health
  5. Association for International Cancer Research
  6. Ferrari Foundation
  7. Monzino Foundation
  8. CARIPLO Foundation
  9. Fondazione Piemontese per la Ricerca sul Cancro-ONLUS-Intramural grant [5X1000 2008]

向作者/读者索取更多资源

Background: Integrin-mediated adhesion of cells to the extracellular matrix (ECM) relies on the dynamic formation of focal adhesions (FAs), which are biochemical and mechanosensitive platforms composed of a large variety of cytosolic and transmembrane proteins. During migration, there is a constant turnover of ECM contacts that initially form as nascent adhesions at the leading edge, mature into FAs as actomyosin tension builds up, and are then disassembled at the cell rear, thus allowing for cell detachment. Although the mechanisms of FA assembly have largely been defined, the molecular circuitry that regulates their disassembly still remains elusive. Results: Here, we show that RN-tre, a GTPase-activating protein (GAP) for Rabs including Rab5 and Rab43, is a novel regulator of FA dynamics and cell migration. RN-tre localizes to FAs and to a pool of Rab5-positive vesicles mainly associated with FAs undergoing rapid remodeling. We found that RN-tre inhibits endocytosis of beta 1, but not beta 3, integrins and delays the turnover of FAs, ultimately impairing beta 1-dependent, but not beta 3-dependent, chemotactic cell migration. All of these effects are mediated by its GAP activity and rely on Rab5. Conclusions: Our findings identify RN-tre as the Rab5-GAP that spatiotemporally controls FA remodeling during chennotactic cell migration.

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