title: Dictyostelium ACAP-A is an ArfGAP involved in cytokinesis, cell migration and actin cytoskeleton dynamics.
abstract: ACAPs and ASAPs are Arf-GTPase-activating proteins with BAR, PH, GAP and ankyrin repeat domains and are known to regulate vesicular traffic and actin cytoskeleton dynamics in mammalian cells. The amoeba Dictyostelium has only two proteins with this domain organization, instead of the six in human, enabling a more precise functional analysis. Genetic invalidation of acapA resulted in multinucleated cells with cytokinesis defects. Mutant acapA(-) cells were hardly motile and their multicellular development was significantly delayed. In addition, formation of filopodial protrusions was deficient in these cells. Conversely, re-expression of ACAP-A-GFP resulted in numerous and long filopodia-like protrusions. Mutagenesis studies showed that the ACAP-A actin remodeling function was dependent on its ability to activate its substrate, the small GTPase ArfA. Likewise, the expression of a constitutively active ArfA•GTP mutant in wild-type cells led to a significant reduction in filopodia length. Together, our data support a role for ACAP-A in the control of the actin cytoskeleton organization and dynamics through an ArfA-dependent mechanism.
authors.affiliation: Département de Physiologie Cellulaire et Métabolisme, Centre Médical Universitaire, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Dias
authors.forename: Cédric
authors.initials: C
authors.lastname: Blanc
authors.forename: Nelcy
authors.initials: N
authors.lastname: Thazar-Poulot
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ben Larbi
authors.forename: Pierre
authors.initials: P
authors.lastname: Cosson
authors.forename: François
authors.initials: F
authors.lastname: Letourneur
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000235:genetics; D048749:Cytokinesis / Q000235:genetics; D004023:Dictyostelium / Q000201:enzymology / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation / Q000235:genetics; D011554:Pseudopodia / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: D000199:Actins; D020690:GTPase-Activating Proteins; D034741:RNA, Small Interfering