title: Phosphorylation of ACAP1 by Akt regulates the stimulation-dependent recycling of integrin beta1 to control cell migration.
abstract: 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 beta1 to control cell migration. However, in contrast to TfR recycling, the role of ACAP1 in beta1 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 beta1, inhibits beta1 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.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Ballif
authors.forename: Aimee M
authors.initials: AM
authors.lastname: Powelka
authors.forename: Jun
authors.initials: J
authors.lastname: Dai
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.forename: Victor W
authors.initials: VW
authors.lastname: Hsu
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism
chemical_list: C507017:ACAP1 protein, human; D000089982:ADP-Ribosylation Factor 6; D020690:GTPase-Activating Proteins; D019012:Integrin beta1; D011990:Receptors, Transferrin; D051057:Proto-Oncogene Proteins c-akt; D020727:ADP-Ribosylation Factors