Bidirectional modulation of transmitter release by calcium channel/syntaxin interactions in vivo.
Protein interactions within the active zone of the nerve terminal are critical for regulation of transmitter release. The SNARE protein syntaxin 1A, primarily known for important interactions that control vesicle fusion, also interacts with presynaptic voltage-gated calcium channels. Based on recordings of calcium channel function in vitro, it has been hypothesized that syntaxin 1A-calcium channel interactions could alter calcium channel function at synapses. However, results at synapses in vitro suggest two potentially opposing roles: enhancement of neurotransmitter release by positioning docked vesicles near calcium channels and inhibition of calcium channel function by interaction with SNARE proteins. We have examined the possibility that these two effects of syntaxin can occur at synapses by studying the effects on transmitter release of manipulating syntaxin 1A-calcium channel interactions at Xenopus tadpole tail neuromuscular synapses in vivo. Introduction of synprint peptides, which competitively perturb syntaxin 1A-calcium channel interactions, decreased quantal content at these synapses and increased paired-pulse and tetanic facilitation. In contrast, injecting mRNA for mutant (A240V, V244A) syntaxin 1A, which reduces calcium channel modulation but not binding in vitro, increased quantal content and decreased paired-pulse and tetanic facilitation. Injection of wild-type syntaxin 1A mRNA had no effect. The opposing effects of synprint peptides and mutant syntaxin 1A provide in vivo support for the hypothesis that these interactions serve both to colocalize calcium channels with the release machinery and to modulate the functional state of the calcium channel. As such, these two effects of syntaxin on calcium channels modulate transmitter release in a bidirectional manner.
Keith
Ryan K
RK
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Poage
Robert E
RE
Yokoyama
Charles T
CT
Catterall
William A
WA
Meriney
Stephen D
SD
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D050765:Qa-SNARE Proteins / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*; D014981:Xenopus
D015220:Calcium Channels; D018377:Neurotransmitter Agents; D050765:Qa-SNARE Proteins