IPF, a vesicular uptake inhibitory protein factor, can reduce the Ca(2+)-dependent, evoked release of glutamate, GABA and serotonin.
Synaptic vesicles in the nerve terminal play a pivotal role in neurotransmission. Neurotransmitter accumulation into synaptic vesicles is catalyzed by distinct vesicular transporters, harnessing an electrochemical proton gradient generated by V-type proton-pump ATPase. However, little is known about regulation of the transmitter pool size, particularly in regard to amino acid neurotransmitters. We previously provided evidence for the existence of a potent endogenous inhibitory protein factor (IPF), which causes reduction of glutamate and GABA accumulation into isolated, purified synaptic vesicles. In this study we demonstrate that IPF is concentrated most in the synaptosomal cytosol fraction and that, when introduced into the synaptosome, it leads to a decrease in calcium-dependent exocytotic (but not calcium-independent) release of glutamate in a concentration-dependent manner. In contrast, alpha-fodrin (non-erythroid spectrin), which is structurally related to IPF and thought to serve as the precursor for IPF, is devoid of such inhibitory activity. Intrasynaptosomal IPF also caused reduction in exocytotic release of GABA and the monoamine neurotransmitter serotonin. Whether IPF affects vesicular storage of multiple neurotransmitters in vivo would depend upon the localization of IPF. These results raise the possibility that IPF may modulate synaptic transmission by acting as a quantal size regulator of one or more neurotransmitters.
Tamura
Y
Y
Mental Health Research Institute, The University of Michigan, Ann Arbor, Michigan, USA.
Ozkan
E D
ED
Bole
D G
DG
Ueda
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005089:Exocytosis / Q000187:drug effects; D005615:Freezing; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism* / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D033921:Vesicular Transport Proteins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D013049:Spectrin
D002118:Calcium; D002352:Carrier Proteins; D004121:Dimethyl Sulfoxide; D018698:Glutamic Acid; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D012701:Serotonin; D033921:Vesicular Transport Proteins; D005680:gamma-Aminobutyric Acid; D013049:Spectrin; C422208:Sptan1 protein, rat