Phosphorylation of ACAP1 by Akt regulates the stimulation-dependent recycling of integrin β1 to control cell migration

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 beta 1 to control cell migration. However, in contrast to TfR recycling, the role of ACAP1 in beta 1 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 beta 1, inhibits beta 1 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.