title: Arf GAPs: A family of proteins with disparate functions that converge on a common structure, the integrin adhesion complex.
abstract: ADP-ribosylation factors (Arfs) are members of the Ras GTPase superfamily. The function of Arfs is dependent on GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. Arf GAPs have been shown to be present in integrin adhesion complexes, which include focal adhesions. Integrin adhesion complexes are composed of integrins, scaffolding proteins and signaling proteins and regulate cell proliferation, survival, differentiation and migration. Understanding the role of Arf GAPs in the regulation of integrin adhesion complexes is relevant to understanding normal physiology and cancer. In this review, we will discuss the contribution of the Arf GAP family members to the regulation of integrin adhesion complexes, examining the diverse mechanisms by which they control integrin adhesion complex formation, maturation and dissolution. GIT1 and ARAP2 serve as GAPs for Arf6, regulating Rac1 and other effectors by mechanisms still being defined. In contrast, GIT2 regulates Rac1 independent of Arf6. AGAP2 binds to and regulates focal adhesion kinase (FAK). ARAP2 and ACAP1, both Arf6 GAPs, regulate membrane trafficking of integrins through different endocytic pathways, exerting opposite effects on focal adhesions. ASAP1 not only regulates actin cytoskeleton remodeling through its interaction with nonmuscle myosin 2A, but is also important in integrin recycling. These examples illustrate the diversity and versatility of Arf GAPs as regulators of integrin adhesion complex structure and function.
authors.affiliation: a Laboratory of Cell and Molecular Biology , National Cancer Institute, National Institutes of Health , Bethesda , MD , USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Vitali
authors.affiliation: a Laboratory of Cell and Molecular Biology , National Cancer Institute, National Institutes of Health , Bethesda , MD , USA.
authors.forename: Sofia
authors.initials: S
authors.lastname: Girald-Berlingeri
authors.affiliation: a Laboratory of Cell and Molecular Biology , National Cancer Institute, National Institutes of Health , Bethesda , MD , USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Randazzo
authors.affiliation: b Department of Biology , Williams College , Williamstown , MA , USA.
authors.forename: Pei-Wen
authors.identifier: 0000-0001-5102-9709
authors.initials: PW
authors.lastname: Chen
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000818:Animals; D004705:Endocytosis; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D020727:ADP-Ribosylation Factors
keywords: ADP-ribosylation factor GTPase-activating protein; ADP-ribosylation factors; ARAP2; ASAP1; GIT1/2; Integrin adhesion complex