Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

The 25-kDa synaptosome-associated protein (SNAP-25) binds and inhibits delayed rectifier potassium channels in secretory cells.

Authors: Ji, J  Tsuk, S  Salapatek, AM  Huang, X  Chikvashvili, D  Pasyk, EA  Kang, Y  Sheu, L  Tsushima, R  Diamant, N  Trimble, WS  Lotan, I  Gaisano, HY 
Citation: Ji J, etal., J Biol Chem 2002 Jun 7;277(23):20195-204. Epub 2002 Mar 29.
Pubmed: (View Article at PubMed) PMID:11925439
DOI: Full-text: DOI:10.1074/jbc.M201034200

Delayed-rectifier K(+) channels (K(DR)) are important regulators of membrane excitability in neurons and neuroendocrine cells. Opening of these voltage-dependent K(+) channels results in membrane repolarization, leading to the closure of the Ca(2+) channels and cessation of insulin secretion in neuroendocrine islet beta cells. Using patch clamp techniques, we have demonstrated that the activity of the K(DR) channel subtype, K(V)1.1, identified by its specific blocker dendrodotoxin-K, is inhibited by SNAP-25 in insulinoma HIT-T15 beta cells. A co-precipitation study of rat brain confirmed that SNAP-25 interacts with the K(V)1.1 protein. Cleavage of SNAP-25 by expression of botulinum neurotoxin A in HIT-T15 cells relieved this SNAP-25-mediated inhibition of K(DR). This inhibitory effect of SNAP-25 is mediated by the N terminus of K(V)1.1, likely by direct interactions with K(Valpha)1.1 and/or K(V)beta subunits, as revealed by co-immunoprecipitation performed in the Xenopus oocyte expression system and in vitro binding. Taken together we have concluded that SNAP-25 mediates secretion not only through its participation in the exocytotic SNARE complex but also by regulating membrane potential and calcium entry through its interaction with K(DR) channels.

Annotation

Objects referenced in this article

Additional Information

 
CRRD Object Information
CRRD ID: 1299041
Created: 2004-06-01
Species: All species
Last Modified: 2006-04-25
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.