Newly synthesized phosphatidylinositol phosphates are required for synaptic norepinephrine but not glutamate or gamma-aminobutyric acid (GABA) release.
Newly synthesized phosphatidylinositol phosphates have been implicated in many membrane-trafficking reactions. They are essential for exocytosis of norepinephrine in PC12 cells and chromaffin cells, suggesting a function in membrane fusion. We have now studied the role of phosphatidylinositol phosphates in synaptic vesicle exocytosis using synaptosomes. Under conditions where phosphorylation of phosphatidylinositols is blocked, norepinephrine secretion was nearly abolished whereas glutamate and GABA release was still elicited. Thus phosphatidylinositides are essential only for some membrane fusion reactions, and exocytotic release mechanisms differ between neurotransmitters.
Center for Basic Neuroscience, Department of Molecular Genetics and Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
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Khvotchev
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Südhof
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D019439:Chromaffin Cells / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis; D018698:Glutamic Acid / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D016716:PC12 Cells; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000096:biosynthesis; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis*; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001152:Arsenicals; D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; C029341:oxophenylarsine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002118:Calcium; D009638:Norepinephrine