Regulation of integrin trafficking by PEA-15

Abstract

Integrins function as adhesion receptors that mediate signaling between the cytoskeleton and extracellular matrix. Integrin activation initiates signaling that regulates morphology, matrix remodeling, cell survival, and ultimately cell motility. Recently, more focus has been devoted to the endosomal trafficking of integrins and how this contributes to cell motility. Recycling of internalized integrins in particular is required for invasion of cancer cells in 3D environments. We present here observations of Phosphoprotein Enriched in Astrocytes of 15 kDa (PEA-15) which show that it is an endosomal protein. We show that PEA-15 is localized in endosomes in multiple cell types. We also show that PEA-15 interacts with microtubules in a manner dependent on PEA-15 phosphorylation. Our data also indicate that PEA-15 is required for efficient endosomal recycling of internalized α5β1 integrin, also in a manner dependent on PEA-15 phosphorylation. PEA-15 also co-traffics with internalized active α5β1 integrin and sorts β integrins to early endosomes. These observations suggest a novel cytoskeletal and endosomal context for PEA-15 function in the control of cell motility. Perhaps more importantly, it provides a new perspective for the interpretation of PEA-15-mediated processes in the cell.