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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/18249

Title: Syntaxin-1A Inhibits the KATP Channel Through Interaction with Distinct Sites Along the Nucleotide-binding Folds of Sulfonylurea Receptor 1
Authors: Chang, Nathan
Advisor: Gaisano, Herbert Young
Feng, Zhong-Ping
Department: Physiology
Keywords: Syntaxin-1A
KATP
nucleotide-binding folds
ATP/ADP
Issue Date: 13-Jan-2010
Abstract: The KATP channel is a key regulator of the pancreatic β-cell, effectively linking metabolic status to electrical activity. Syntaxin-1A has been previously reported by our lab to both bind and inhibit the KATP channel via the nucleotide-binding folds (NBFs). The purpose of this thesis project was to elucidate the precise regions within the NBFs responsible for the Syn-1A- KATP interaction. In vitro binding assays revealed that Syn-1A associates with the Walker domains of both NBF1 and NBF2. Furthermore, site directed mutagenesis of the conserved lysine in Walker A of both NBFs abolishes Syn-1A affinity for this region. Electrophysiological recordings indicate that channel inhibition was mediated primarily through interaction with NBF1-Walker B and both Walkers of NBF2. Based on these results, we propose a model by which Syn-1A acts as an inhibitory clamp on the KATP channel, effectively buffering minor fluctuations in ATP/ADP concentration to prevent unnecessary channel activity.
URI: http://hdl.handle.net/1807/18249
Appears in Collections:Master
Department of Physiology - Master theses

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