Acaps Are Arf6 Gtpase-Activating Proteins That Function in the Cell Periphery
| Autor: | Jianlan Sun, Koichi Miura, Fraser D. Brown, Julie G. Donaldson, Zhongzhen Nie, Victor W. Hsu, Letizia Foroni, Paul A. Randazzo, Trevor R. Jackson |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate Cytoplasm GTPase-activating protein ADP ribosylation factor Molecular Sequence Data Phosphatidic Acids membrane traffic Biology Arginine Guanosine Diphosphate Substrate Specificity GTPase-activating proteins Cell membrane Fluorides Mice pleckstrin homology domain medicine Animals Humans Amino Acid Sequence Aluminum Compounds Cytoskeleton Conserved Sequence Actin Platelet-Derived Growth Factor Sequence Homology Amino Acid ADP-Ribosylation Factors Phospholipase D Cell Membrane 3T3 Cells Cell Biology Actin cytoskeleton Actins Cell biology Pleckstrin homology domain ADP-ribosylation factor medicine.anatomical_structure Amino Acid Substitution ADP-Ribosylation Factor 6 Multigene Family Original Article Cell Surface Extensions Carrier Proteins Sequence Alignment actin HeLa Cells |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.151.3.627 |
| Popis: | The GTP-binding protein ADP-ribosylation factor 6 (Arf6) regulates endosomal membrane trafficking and the actin cytoskeleton in the cell periphery. GTPase-activating proteins (GAPs) are critical regulators of Arf function, controlling the return of Arf to the inactive GDP-bound state. Here, we report the identification and characterization of two Arf6 GAPs, ACAP1 and ACAP2. Together with two previously described Arf GAPs, ASAP1 and PAP, they can be grouped into a protein family defined by several common structural motifs including coiled coil, pleckstrin homology, Arf GAP, and three complete ankyrin-repeat domains. All contain phosphoinositide-dependent GAP activity. ACAP1 and ACAP2 are widely expressed and occur together in the various cultured cell lines we examined. Similar to ASAP1, ACAP1 and ACAP2 were recruited to and, when overexpressed, inhibited the formation of platelet-derived growth factor (PDGF)–induced dorsal membrane ruffles in NIH 3T3 fibroblasts. However, in contrast with ASAP1, ACAP1 and ACAP2 functioned as Arf6 GAPs. In vitro, ACAP1 and ACAP2 preferred Arf6 as a substrate, rather than Arf1 and Arf5, more so than did ASAP1. In HeLa cells, overexpression of either ACAP blocked the formation of Arf6-dependent protrusions. In addition, ACAP1 and ACAP2 were recruited to peripheral, tubular membranes, where activation of Arf6 occurs to allow membrane recycling back to the plasma membrane. ASAP1 did not inhibit Arf6-dependent protrusions and was not recruited by Arf6 to tubular membranes. The additional effects of ASAP1 on PDGF-induced ruffling in fibroblasts suggest that multiple Arf GAPs function coordinately in the cell periphery. |
| Databáze: | OpenAIRE |
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