Regulation of AP-3 Function by Inositides

摘要: Abstract As part of the growing effort to understand role inositol phosphates and lipids play in regulation vesicle traffic within nerve terminals, we determined whether or not synapse-specific clathrin assembly protein AP-3 can interact with lipids. We found that soluble dioctanoyl-phosphatidylinositol 3,4,5-trisphosphate (DiC8PtdIns(3,4,5)P3) was only 7.5-fold weaker a ligand than D-myo-inositol hexakisphosphate assays measured displacement D-myo-[3H]inositol hexakisphosphate. In functional both these ligands inhibited assembly, but DiC8-PtdIns(3,4,5)P3 more potent exhibited larger maximal effect. also examined structural features establish specificity. Dioctanoyl-phosphatidylinositol 3,4-bisphosphate, which does have 5-phosphate, 4,5-O-bisphosphoryl-D-myo-inosityl 1-O-(1,2-O-diundecyl)-sn-3-glycerylphosphate, 3-phosphate, were, respectively, 2-fold 4-fold less as inhibitors assembly. Deacylation reduced its affinity for almost 20-fold, dramatically lowered ability inhibit The deacylated products derivatives phosphatidylinositol 3,4-bisphosphate 4,5-bisphosphate were significant It therefore appears interactions inositides should be considered simply terms electrostatic effects highly charged phosphate groups. Ligand specificity mediated by hydrophobic fatty-acyl chains