Referenced in: none

Automatically associated channels: ClC2 , ClC4

Title: Evidence for a functional interaction between the ClC-2 chloride channel and the retrograde motor dynein complex.

Authors: Sonja U Dhani, Raha Mohammad-Panah, Najma Ahmed, Cameron Ackerley, Mohabir Ramjeesingh, Christine E Bear

Journal, date & volume: J. Biol. Chem., 2003 May 2 , 278, 16262-70

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12601004

Abstract
The ClC-2 chloride channel has been implicated in essential physiological functions. Analyses of ClC-2 knock-out mice suggest that ClC-2 expression in retinal pigment epithelia and Sertoli cells normally supports the viability of photoreceptor cells and male germ cells, respectively. Further, other studies suggest that ClC-2 expression in neurons may modify inhibitory synaptic transmission via the gamma-aminobutyric acid, type A receptor. However, complete understanding of the physiological functions of ClC-2 requires elucidation of the molecular basis for its regulation. Using cell imaging and biochemical and electrophysiological techniques, we show that expression of ClC-2 at the cell surface may be regulated via an interaction with the dynein motor complex. Mass spectrometry and Western blot analysis of eluate from a ClC-2 affinity matrix showed that heavy and intermediate chains of dynein bind ClC-2 in vitro. The dynein intermediate chain co-immunoprecipitates with ClC-2 from hippocampal membranes suggesting that they also interact in vivo. Disruption of dynein motor function perturbs ClC-2 localization and increases the functional expression of ClC-2 in the plasma membranes of COS7 cells. Thus, cell surface expression of ClC-2 may be regulated by dynein motor activity. This work is the first to demonstrate an in vivo interaction between an ion channel and the dynein motor complex.