The surprising catch of a voltage-gated potassium channel in a neuronal SNARE.
Among ion channels, voltage-gated calcium channels have been considered unique in their ability to mediate signaling events independent of the flow of ions through their pore. A voltage-gated potassium channel termed Kv2.1 has been identified as playing a role remarkably similar to one ion-independent function of calcium channels, facilitating regulated exocytosis through a direct interaction with a t-SNARE [soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor] component of the vesicle release machinery. Kv2.1 overexpression enhances depolarization-induced secretion from the neuroendocrine-like PC12 cell line, and a nonconducting Kv2.1 mutant can accomplish the same feat. Kv2.1 interacts directly with syntaxin 1A, a plasma membrane t-SNARE component of the vesicle docking and fusion apparatus. Deletion of the syntaxin 1A-binding segment from Kv2.1 abolishes its ability to promote vesicle release, supporting a mechanism whereby Kv2.1 presumably transfers voltage-dependent conformational changes induced by membrane depolarization to interacting t-SNAREs to affect exocytosis. Kv2.1, a major mediator of electrical events in central neurons, cardiac and smooth muscle, and pancreatic beta cells, must now also be recognized as a physical mediator of secretion. That Kv2.1 is phosphorylated at numerous sites within the syntaxin 1A binding segment raises the possibility that its role in secretion may be dynamically regulated by diverse signaling events.
Mohapatra
Durga P
DP
Department of Pharmacology, School of Medicine, University of California, Davis, CA 95616, USA.
Vacher
Helene
H
Trimmer
James S
JS
D000818:Animals; D005089:Exocytosis; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D051381:Rats; D050600:SNARE Proteins / Q000378:metabolism*; D050827:Syntaxin 1 / Q000378:metabolism
D024642:Potassium Channels, Voltage-Gated; D050600:SNARE Proteins; D050827:Syntaxin 1