title: ARAP1 regulates the ring size of circular dorsal ruffles through Arf1 and Arf5.
abstract: Small guanosine triphosphatase (GTPase) ADP-ribosylation factors (Arfs) regulate membrane traffic and actin reorganization under the strict control of GTPase-activating proteins (GAPs). ARAP1 (Arf GAP with Rho GAP domain, ankyrin repeat, and PH domain 1) is an Arf GAP molecule with multiple PH domains that recognize phosphatidylinositol 3,4,5-trisphosphate. We found that growth factor stimulation induced localization of ARAP1 to an area of the plasma membrane inside the ring structure of circular dorsal ruffles (CDRs). Moreover, expression of ARAP1 increased the size of the CDR filamentous-actin ring in an Arf GAP activity-dependent manner, whereas smaller CDRs were formed by ARAP1 knockdown. In addition, expression of a dominant-negative mutant of Arf1 and Arf5, the substrates of ARAP1, expanded the size of CDRs, suggesting that the two Arf isoforms regulate ring structure downstream of ARAP1. Therefore our results reveal a novel molecular mechanism of CDR ring size control through the ARAP1-Arf1/5 pathway.
authors.affiliation: Division of Membrane Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Hasegawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Tsujita
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
authors.forename: Toshiki
authors.initials: T
authors.lastname: Itoh
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism*; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000818:Animals; D000077214:Becaplermin; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021961:Cell Membrane Structures / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010873:Pinocytosis; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D020574:Proto-Oncogene Proteins c-sis / Q000502:physiology; D034622:RNA Interference; D059008:Time-Lapse Imaging
chemical_list: C446513:ARAP1 protein, human; D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors; C116691:ARF5 protein, human