Developmental Cell
Volume 9, Issue 5, November 2005, Pages 663-673
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Article
Phosphorylation of ACAP1 by Akt Regulates the Stimulation-Dependent Recycling of Integrin β1 to Control Cell Migration

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Summary

Components of intracellular signaling that mediate the stimulation-dependent recycling of integrins are being identified, but key transport effectors that are the ultimate downstream targets remain unknown. ACAP1 has been shown recently to function as a transport effector in the cargo sorting of transferrin receptor (TfR) that undergoes constitutive recycling. We now show that ACAP1 also participates in the regulated recycling of integrin β1 to control cell migration. However, in contrast to TfR recycling, the role of ACAP1 in β1 recycling requires its phosphorylation by Akt, which is, in turn, regulated by a canonical signaling pathway. Disrupting the activities of either ACAP1 or Akt, or their assembly with endosomal β1, inhibits β1 recycling and cell migration. These findings advance an understanding of how integrin recycling is achieved during cell migration, and also address a basic issue of how intracellular signaling can interface with transport to achieve regulated recycling.

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