Functional impact of syntaxin on gating of N-type and Q-type calcium channels.
Rapid and reliable synaptic transmission depends upon the close proximity of voltage-gated calcium channels and neurotransmitter-containing vesicles in the presynaptic terminal. Although it is clear that a local Ca2+ rise conveys the crucial signal from Ca2+ channels to the exocytotic mechanism, little is known about whether communication ever proceeds in the opposite direction, from the release machinery to Ca2+ channels. To look for such signalling, we examined the interaction of various types of voltage-gated Ca2+ channels with syntaxin, a presynaptic membrane protein of relative molecular mass 35,000 which may play a key part in synaptic vesicle docking and fusion and which interacts strongly with N-type Ca2+ channels. Here we report that co-expression of syntaxin 1A with N-type channels in Xenopus oocytes sharply decreases the availability of these channels. This is due to the stabilization of channel inactivation rather than to a simple block or lack of channel expression, because it is overcome by strong hyperpolarization. Deletion of syntaxin's carboxy-terminal transmembrane domain abolishes its functional effect on Ca2+ channels. Syntaxin produced a similar effect on Q-type Ca2+ channels encoded by alpha 1A but not on L-type Ca2+ channels. Thus, the syntaxin effect is specific for Ca2+ channel types that participate in fast transmitter release in the mammalian central nervous system. We hypothesize that, in addition to acting as a vesicle-docking site, syntaxin may influence presynaptic Ca2+ channels, opposing Ca2+ entry where it is not advantageous, but allowing it at release sites where synaptic vesicles have become docked and/or ready for fusion.
Bezprozvanny
I
I
Department of Molecular and Cellular Physiology, Stanford University Medical Center, California 94305, USA.
Scheller
R H
RH
Tsien
R W
RW
D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D015640:Ion Channel Gating; D008564:Membrane Potentials; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009865:Oocytes; D018075:RNA, Complementary / Q000235:genetics; D013572:Synaptic Vesicles / Q000378:metabolism; D050827:Syntaxin 1; D014981:Xenopus
D000954:Antigens, Surface; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D018075:RNA, Complementary; D050827:Syntaxin 1; D002118:Calcium