title: Phosphoinositide binding by par-3 involved in par-3 localization.
abstract: Electrostatic interactions between lipids and proteins control many cellular events. We found that phospholipids, including phosphatidylinositol 3-phosphate, phosphatidylinositol 4,5-bisphosphate, and phosphatidylinositol 3,4,5-triphosphate, bound to the C-terminal coiled-coil region of par-3 at conserved, basic residues. We identified K1013 and K1014 as the phosphoinositide binding site, because the K1013E/K1014E mutation of rat par-3 abolished its lipid binding. Importantly, the K1013E/K1014E par-3 mutant exhibited significantly weaker localization at the cell-cell junctions than the wild-type par-3. Fluorescence recovery after photo-bleaching analyses confirmed the faster turnover of mutant par-3 at cell-cell junctions. The treatment of cells with an inhibitor of phosphatidylinositol 3-kinases partially increased the turnover of par-3. These data suggested that the putative phospholipid binding by par-3 is important for its localization at cell-cell junctions.
authors.affiliation: Laboratory of Membrane and Cytoskeleton Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Horikoshi
authors.forename: Sayaka
authors.initials: S
authors.lastname: Hamada
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
authors.forename: Shiro
authors.initials: S
authors.lastname: Suetsugu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism / Q000648:ultrastructure; D008081:Liposomes / Q000737:chemistry; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D002352:Carrier Proteins; D008081:Liposomes; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011994:Recombinant Proteins; C472451:Pard3 protein, rat