Abstract
Despite the fact that inositol hexakisphosphate (InsP(6)) is the most abundant inositol metabolite in cells, its cellular function has remained an enigma. In the present study, we present the first evidence of a protein kinase identified in rat cerebral cortex/hippocampus that is activated by InsP(6). The substrate for the InsP(6)-regulated protein kinase was found to be the synaptic vesicle-associated protein, pacsin/syndapin I. This brain-specific protein, which is highly enriched at nerve terminals, is proposed to act as a molecular link coupling components of the synaptic vesicle endocytic machinery to the cytoskeleton. We show here that the association between pacsin/syndapin I and dynamin I can be increased by InsP(6)-dependent phosphorylation of pacsin/syndapin I. These data provide a model by which InsP(6)-dependent phosphorylation regulates synaptic vesicle recycling by increasing the interaction between endocytic proteins at the synapse.
Highlights
A large number of G-protein-coupled and growth factor receptors activate phospholipase C to stimulate the hydrolysis of the phospholipid, phosphatidylinositol 4,5-bisphosphate, producing inositol 1,4,5-trisphosphate (InsP3)1 and diacylglycerol
InsP6 in synaptic vesicle trafficking has emerged from studies showing that InsP6 binds with high affinity to a number of proteins that are involved in exo/endocytosis including the clathrin assembly proteins AP2 and AP3 and the synaptic vesicle calcium-sensing protein synaptotagmin (9 –12)
We have investigated the possibility of the existence of a protein kinase that is regulated by InsP6
Summary
InsP3, inositol 1,4,5-trisphosphate; InsP4, inositol 1,3,4,5-tetrakisphosphate; InsP6, inositol 1,2,3,4,5,6-hexakisphosphate; PP-InsP3, diphosphoinositol pentakisphosphate; GST, glutathione S-transferase; PAGE, polyacrylamide gel electrophoresis; MALDI-TOF, matrix-assisted laser desorption ionization-time-of-flight. InsP6 in synaptic vesicle trafficking has emerged from studies showing that InsP6 binds with high affinity to a number of proteins that are involved in exo/endocytosis including the clathrin assembly proteins AP2 and AP3 and the synaptic vesicle calcium-sensing protein synaptotagmin (9 –12). We have investigated the possibility of the existence of a protein kinase that is regulated by InsP6. We found that the pacsin/syndapin I, a synaptic vesicle-associated protein that acts as a molecular link coupling the endocytic machinery to the cytoskeleton, is phosphorylated by a protein kinase that is regulated by InsP6. InsP6-regulated phosphorylation of pacsin/syndapin I increases the interaction between pacsin/syndapin I and dynamin I. These data provide a novel model by which InsP6 can regulate synaptic vesicle endocytosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
