Modulation of the SNARE core complex by dopamine.
Communication between nerve cells in the brain occurs primarily through specialized junctions called synapses. Recently, many details of synaptic transmission have emerged. The identities of specific proteins important for synaptic vesicle release have now been established. We have investigated three synaptic proteins, VAMP (vesicle associated membrane protein; also called synaptobrevin), syntaxin, and SNAP25 (synaptosomal associated protein of 25kDa) as possible targets in the dopamine-mediated modulation of synaptic function in rat striatal slices. These three proteins form a SNARE (soluble N-ethylmalemide-sensitive factor attachment protein receptors) core complex that is known to be essential for synaptic transmission. Although it is envisioned that the SNAREs undergo dynamic and cyclic interactions to elicit synaptic vesicle release, their precise functions in neurotransmission remains unknown. We have examined SNARE complexes in intact rat striatal slices. Cellular proteins were solubilized, separated electrophoretically by SDS-PAGE, and then identified immunologically. Application of dopamine to striatal slices results in SNAREs favoring the SNARE core complex, a complex which forms spontaneously in the absence of crosslinking agents, rather than the monomer form. In addition, rapid crosslinking of dopamine-treated striatal slices demonstrates that the SNARE complex is increased 4 fold in dopamine treated striatal slices compared with control slices. Haloperidol blocked the dopamine-induced change in the core complex. These results suggest that changes in the activities of SNAREs may be involved in the underlying cellular mechanisms(s) of dopamine-regulated synaptic plasticity of the striatum.
Fisher
H
H
Department of Physiology and Biophysics, Neuroscience Research Group, The University of Calgary, Canada.
Braun
J E
JE
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008565:Membrane Proteins / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D050600:SNARE Proteins; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D033921:Vesicular Transport Proteins
D002316:Cardiotonic Agents; D018492:Dopamine Antagonists; D008565:Membrane Proteins; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D006220:Haloperidol; D004298:Dopamine