title: Cooperation of phosphoinositides and BAR domain proteins in endosomal tubulation.
abstract: Phosphorylated derivatives of phosphatidylinositol (PtdIns) regulate many intracellular events, including vesicular trafficking and actin remodeling, by recruiting proteins to their sites of function. PtdIns(4,5)-bisphosphate [PI(4,5)P2] and related phosphoinositides are mainly synthesized by type I PtdIns-4-phosphate 5-kinases (PIP5Ks). We found that PIP5K induces endosomal tubules in COS-7 cells. ADP-ribosylation factor (ARF) 6 has been shown to act upstream of PIP5K and regulate endocytic transport and tubulation. ARF GAP with coiled-coil, ankyrin repeat, and pleckstrin homology domains 1 (ACAP1) has guanosine triphosphatase-activating protein (GAP) activity for ARF6. While there were few tubules induced by the expression of ACAP1 alone, numerous endosomal tubules were induced by coexpression of PIP5K and ACAP1. ACAP1 has a pleckstrin homology (PH) domain known to bind phosphoinositide and a Bin/amphiphysin/Rvs (BAR) domain that has been reported to detect membrane curvature. Truncated and point mutations in the ACAP1 BAR and PH domains revealed that both BAR and PH domains are required for tubulation. These results suggest that two ARF6 downstream molecules, PIP5K and ACAP1, function together in endosomal tubulation and that phosphoinositide levels may regulate endosomal dynamics.
authors.affiliation: Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Tokyo 153-8904, Japan.
authors.forename: Naeko
authors.initials: N
authors.lastname: Shinozaki-Narikawa
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Shibasaki
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D054803:Phospholipase C delta; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014404:Tubulin / Q000378:metabolism; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism
chemical_list: C507017:ACAP1 protein, human; D000089982:ADP-Ribosylation Factor 6; D020690:GTPase-Activating Proteins; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D011993:Recombinant Fusion Proteins; D014404:Tubulin; C075637:amphiphysin; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D010738:Type C Phospholipases; D054803:Phospholipase C delta; C000715348:ARF6 protein, human; C000715727:Arf6 protein, mouse; D015739:Nocodazole