alpha V beta 3 and alpha 5B1 integrin recycling pathways dictate downstream Rho kinase signaling to regulate persistent cell migration

White, D., Caswell, P. and Norman, J. (2007) alpha V beta 3 and alpha 5B1 integrin recycling pathways dictate downstream Rho kinase signaling to regulate persistent cell migration. Journal of Cell Biology, 177(3), pp. 515-525. (doi: 10.1083/jcb.200609004)

Abstract

Accumulating evidence suggests that integrin recycling regulates cell migration. However, the lack of reagents to selectively target the trafficking of individual heterodimers, as opposed to endocytic transport as a whole, has made it difficult to define the contribution made by particular recycling pathways to directional cell movement. We show that autophosphorylation of protein kinase D1 (PKD1) at Ser(916) is necessary for its association with alpha v beta 3 integrin. Expression of PKD1(916A) or the use of mutants of beta 3 that do not bind to PKD1 selectively inhibits short-loop, Rab4-dependent recycling of alpha v beta 3, and this Suppresses the persistence of fibroblast migration. However, we report that short-loop recycling does not directly contribute to fibroblast migration by moving av beta 3 to the cell front, but by antagonizing a5 beta 1 recycling, which, in turn, influences the cell's decision to migrate with persistence or to move randomly.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Norman, Professor James and Caswell, Dr Patrick
• Authors: White, D., Caswell, P., and Norman, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Cell Biology
• ISSN: 1540-8140