The endosomal adaptor protein APPL1 impairs the turnover of leading edge adhesions to regulate cell migration

Joshua A. Broussard, Wan Hsin Lin, Devi Majumdar, Bridget Anderson, Brady Eason, Claire M. Brown, Donna J. Webb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Cell migration is a complex process that requires the integration of signaling events that occur in distinct locations within the cell. Adaptor proteins, which can localize to different subcellular compartments, where they bring together key signaling proteins, are emerging as attractive candidates for controlling spatially coordinated processes. However, their function in regulating cell migration is not well understood. In this study, we demonstrate a novel role for the adaptor protein containing a pleckstrin-homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (APPL1) in regulating cell migration. APPL1 impairs migration by hindering the turnover of adhesions at the leading edge of cells. The mechanism by which APPL1 regulates migration and adhesion dynamics is by inhibiting the activity of the serine/threonine kinase Akt at the cell edge and within adhesions. In addition, APPL1 significantly decreases the tyrosine phosphorylation of Akt by the nonreceptor tyrosine kinase Src, which is critical for Akt-mediated cell migration. Thus, our results demonstrate an important new function for APPL1 in regulating cell migration and adhesion turnover through a mechanism that depends on Src and Akt. Moreover, our data further underscore the importance of adaptor proteins in modulating the flow of information through signaling pathways.

Original languageEnglish (US)
Pages (from-to)1486-1499
Number of pages14
JournalMolecular biology of the cell
Volume23
Issue number8
DOIs
StatePublished - Apr 15 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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