Channelpedia

PubMed 15485870


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv1.4 , Kv3.1 , Kv4.1 , Kv4.2



Title: KChIP3 rescues the functional expression of Shal channel tetramerization mutants.

Authors: Kumud Kunjilwar, Candace Strang, David DeRubeis, Paul J Pfaffinger

Journal, date & volume: J. Biol. Chem., 2004 Dec 24 , 279, 54542-51

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15485870


Abstract
KChIP proteins regulate Shal, Kv4.x, channel expression by binding to a conserved sequence at the N terminus of the subunit. The binding of KChIP facilitates a redistribution of Kv4 protein to the cell surface, producing a large increase in current along with significant changes in channel gating kinetics. Recently we have shown that mutants of Kv4.2 lacking the ability to bind an intersubunit Zn(2+) between their T1 domains fail to form functional channels because they are unable to assemble to tetramers and remain trapped in the endoplasmic reticulum. Here we find that KChIPs are capable of rescuing the function of Zn(2+) site mutants by driving the mutant subunits to assemble to tetramers. Thus, in addition to known trafficking effects, KChIPs play a direct role in subunit assembly by binding to monomeric subunits within the endoplasmic reticulum and promoting tetrameric channel assembly. Zn(2+)-less Kv4.2 channels expressed with KChIP3 demonstrate several distinct kinetic changes in channel gating, including a reduced time to peak and faster entry into the inactivated state as well as extending the time to recover from inactivation by 3-4 fold.