Interaction of syntaxin 1A with the N-terminus of Kv4.2 modulates channel surface expression and gating.

Interaction of syntaxin 1A with the N-terminus of Kv4.2 modulates channel surface expression and gating. Research Abstract Details 

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Interaction of syntaxin 1A with the N-terminus of Kv4.2 modulates channel surface expression and gating. Abstract Text:

Takeshi Yamakawa,Shazahra Saith,Yanan Li,Xiaodong Gao,Herbert Y Gaisano,Robert G Tsushima,

Kv4.2 channels are responsible in the heart for the Ca2+-independent transient outward currents and are important in regulating myocardial excitability and Ca2+ homeostasis. We have identified previously the expression of syntaxin 1A (STX1A) on the cardiac ventricular myocyte plasma membranes, and its modulation of cardiac ATP-sensitive K+ channels. We speculated that STX1A interacts with other cardiac ion channels, thus we examined the interaction of STX1A with Kv4.2 channels. Co-immunoprecipitation and GST pulldown assays demonstrated a direct interaction of STX1A with the Kv4.2 N-terminus. We next investigated the functional alterations of Kv4.2 gating by STX1A in Xenopus oocytes. Coexpression of Kv4.2 with STX1A (1) resulted in a reduction of Kv4.2 current amplitude; (2) caused a depolarizing shift of the steady-state inactivation curve; (3) enhanced the rate of current decay; and (4) accelerated the rate of recovery from inactivation. Additional coexpression of botulinum neurotoxin C, which cleaves STX1A, reversed the effects of STX1A on Kv4.2. STX1A inhibited partially the gating changes by KChIP2, suggesting a competitive interaction of these proteins for an overlapping binding region on the N-terminus of Kv4.2. Indeed, the N-terminal truncation mutants of Kv4.2 (Kv4.2Delta2-40 and Kv4.2Delta7-11), which form part of the KChIP2 binding site, displayed reduced sensitivity to STX1A modulation. Our study suggests that STX1A directly modulates Kv4.2 current amplitude and gating through its interaction with an overlapping region of the KChIP binding motif domain on the Kv4.2 N-terminus.

Interaction of syntaxin 1A with the N-terminus of Kv4.2 modulates channel surface expression and gating. Publishing Authors By Initials

T Yamakawa,S Saith,Y Li,X Gao,HY Gaisano,RG Tsushima,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Interaction of syntaxin 1A with the N-terminus of Kv4.2 modulates channel surface expression and gating. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Biochemistry

VOLUME: 46

Page Numbers: 10942-9

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 29

MONTH: 08

YEAR: 2007

Interaction of syntaxin 1A with the N-terminus of Kv4.2 modulates channel surface expression and gating. Information

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LANGUAGE: eng

NlmUniqueID: 370623

Interaction of syntaxin 1A with the N-terminus of Kv4.2 modulates channel surface expression and gating. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: metabolism

Chemical & Substance for Abstract: Interaction of syntaxin 1A with the N-terminus of Kv4.2 modulates channel surface expression and gating. Information

Substance Name: Syntaxin 1

Registry Number: 0

Grant and Affiliation Information for Interaction of syntaxin 1A with the N-terminus of Kv4.2 modulates channel surface expression and gating.

AFFILIATION: Department of Medicine, University of Toronto, Toronto, Ontario, M5S 1A8 Canada.

Country: United States

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MEDLINETA: Biochemistry

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