Direct interaction of a brain voltage-gated K+ channel with syntaxin 1A: functional impact on channel gating.
Presynaptic voltage-gated K(+) (Kv) channels play a physiological role in the regulation of transmitter release by virtue of their ability to shape presynaptic action potentials. However, the possibility of a direct interaction of these channels with the exocytotic apparatus has never been examined. We report the existence of a physical interaction in brain synaptosomes between Kvalpha1.1 and Kvbeta subunits with syntaxin 1A, occurring, at least partially, within the context of a macromolecular complex containing syntaxin, synaptotagmin, and SNAP-25. The interaction was altered after stimulation of neurotransmitter release. The interaction with syntaxin was further characterized in Xenopus oocytes by both overexpression and antisense knock-down of syntaxin. Direct physical interaction of syntaxin with the channel protein resulted in an increase in the extent of fast inactivation of the Kv1.1/Kvbeta1.1 channel. Syntaxin also affected the channel amplitude in a biphasic manner, depending on its concentration. At low syntaxin concentrations there was a significant increase in amplitudes, with no detectable change in cell-surface channel expression. At higher concentrations, however, the amplitudes decreased, probably because of a concomitant decrease in cell-surface channel expression, consistent with the role of syntaxin in regulation of vesicle trafficking. The observed physical and functional interactions between syntaxin 1A and a Kv channel may play a role in synaptic efficacy and neuronal excitability.
Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, 69978 Ramat-Aviv, Israel.
O
O
Fili
I
I
Michaelevski
Y
Y
Bledi
D
D
Chikvashvili
D
D
Singer-Lahat
H
H
Boshwitz
M
M
Linial
I
I
Lotan
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D005089:Exocytosis / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D051662:Kv1.1 Potassium Channel; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011485:Protein Binding; D021122:Protein Subunits; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25; D013574:Synaptosomes / Q000378:metabolism; D050857:Synaptotagmins; D050827:Syntaxin 1; D014981:Xenopus
D000954:Antigens, Surface; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D050825:Synaptosomal-Associated Protein 25; D050827:Syntaxin 1; D050857:Synaptotagmins; D051662:Kv1.1 Potassium Channel