Regulation of cell surface expression of functional pacemaker channels by a motif in the B-helix of the cyclic nucleotide-binding domain

被引：6

作者：

Nazzari, Hamed ^{[1
]}

Angoli, Damiano ^{[1
]}

Chow, Sarah S. ^{[1
]}

Whitaker, Gina ^{[1
]}

Leclair, Leisha ^{[1
]}

McDonald, Evan ^{[1
]}

Macri, Vincenzo ^{[1
]}

Zahynacz, Kristin ^{[1
]}

Walker, Valerie ^{[1
]}

Accili, Eric A. ^{[1
]}

机构：

[1] Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC V6T 1Z3, Canada

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2008年 / 295卷 / 03期

关键词：

pacemaker channel function; protein export; trafficking; hyperpolarization-activated cyclic nucleotide-gated channel;

D O I：

10.1152/ajpcell.00062.2008

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Previous studies have suggested that a portion of the cyclic nucleotide-binding domain (CNBD) of the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) "pacemaker" channel, composed of the A- and B-helices and the interceding beta-barrel, confers two functions: inhibition of channel opening in response to hyperpolarization and promotion of cell surface expression. The sequence determinants required for each of these functions are unknown. In addition, the mechanism underlying plasma membrane targeting by this subdomain has been limitedly explored. Here we identify a four-amino acid motif (EEYP) in the B-helix that strongly promotes channel export from the endoplasmic reticulum (ER) and cell surface expression but does not contribute to the inhibition of channel opening. This motif augments a step in the trafficking pathway and/or the efficiency of correct folding and assembly.

引用

页码：C642 / C652

页数：11