title: ACAP-A/B are ArfGAP homologs in dictyostelium involved in sporulation but not in chemotaxis.
abstract: Arfs and Arf GTPase-activating proteins (ArfGAPs) are regulators of membrane trafficking and actin dynamics in mammalian cells. In this study, we identified a primordial Arf, ArfA, and two ArfGAPs (ACAP-A/B) containing BAR, PH, ArfGAP and Ankyrin repeat domains in the eukaryote Dictyostelium discoideum. In vitro, ArfA has similar nucleotide binding properties as mammalian Arfs and, with GTP bound, is a substrate for ACAP-A and B. We also investigated the physiological functions of ACAP-A/B by characterizing cells lacking both ACAP-A and B. Although ACAP-A/B knockout cells showed no defects in cell growth, migration or chemotaxis, they exhibited abnormal actin protrusions and approximately 50% reduction in spore yield. We conclude that while ACAP-A/B have a conserved biochemical mechanism and effect on actin organization, their role in migration is not conserved. The absence of an effect on Dictyostelium migration may be due to a specific requirement for ACAPs in mesenchymal migration, which is observed in epithelial cancer cells where most studies of mammalian ArfGAPs were performed.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Chen
authors.forename: Paul A
authors.initials: PA
authors.lastname: Randazzo
authors.forename: Carole A
authors.initials: CA
authors.lastname: Parent
mesh_terms: D000199:Actins / Q000378:metabolism; D002633:Chemotaxis; D004023:Dictyostelium / Q000502:physiology*; D005656:Fungal Proteins / Q000502:physiology*; D013172:Spores, Fungal
chemical_list: D000199:Actins; D005656:Fungal Proteins