K+ channel facilitation of exocytosis by dynamic interaction with syntaxin.
Kv channels inhibit release indirectly by hyperpolarizing membrane potential, but the significance of Kv channel interaction with the secretory apparatus is not known. The Kv2.1 channel is commonly expressed in the soma and dendrites of neurons, where it could influence the release of neuropeptides and neurotrophins, and in neuroendocrine cells, where it could influence hormone release. Here we show that Kv2.1 channels increase dense-core vesicle (DCV)-mediated release after elevation of cytoplasmic Ca2+. This facilitation occurs even after disruption of pore function and cannot be explained by changes in membrane potential and cytoplasmic Ca2+. However, triggering release increases channel binding to syntaxin, a secretory apparatus protein. Disrupting this interaction with competing peptides or by deleting the syntaxin association domain of the channel at the C terminus blocks facilitation of release. Thus, direct association of Kv2.1 with syntaxin promotes exocytosis. The dual functioning of the Kv channel to influence release, through its pore to hyperpolarize the membrane potential and through its C-terminal association with syntaxin to directly facilitate release, reinforces the requirements for repetitive firing for exocytosis of DCVs in neuroendocrine cells and in dendrites.
Singer-Lahat
Dafna
D
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, 69978 Ramat-Aviv, Israel.
Sheinin
Anton
A
Chikvashvili
Dodo
D
Tsuk
Sharon
S
Greitzer
Dafna
D
Friedrich
Reut
R
Feinshreiber
Lori
L
Ashery
Uri
U
Benveniste
Morris
M
Levitan
Edwin S
ES
Lotan
Ilana
I
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D047468:Immunoprecipitation / Q000379:methods; D008564:Membrane Potentials / Q000235:genetics / Q000528:radiation effects; D016296:Mutagenesis / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D009865:Oocytes; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D050765:Qa-SNARE Proteins / Q000378:metabolism*; D051381:Rats; D022142:Secretory Vesicles / Q000187:drug effects / Q000502:physiology*; D051669:Shab Potassium Channels / Q000502:physiology*; D014162:Transfection / Q000379:methods; D014981:Xenopus
D009479:Neuropeptides; D050765:Qa-SNARE Proteins; D051669:Shab Potassium Channels; D049452:Green Fluorescent Proteins; D011189:Potassium Chloride; D002118:Calcium