title: Evidence for a functional interaction between the ClC-2 chloride channel and the retrograde motor dynein complex.
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.
authors.affiliation: Programme in Structural Biology, Research Institute, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 2X8, Canada.
authors.forename: Sonja U
authors.initials: SU
authors.lastname: Dhani
authors.forename: Raha
authors.initials: R
authors.lastname: Mohammad-Panah
authors.forename: Najma
authors.initials: N
authors.lastname: Ahmed
authors.forename: Cameron
authors.initials: C
authors.lastname: Ackerley
authors.forename: Mohabir
authors.initials: M
authors.lastname: Ramjeesingh
authors.forename: Christine E
authors.initials: CE
authors.lastname: Bear
mesh_terms: D000818:Animals; D000090007:CLC-2 Chloride Channels; D019556:COS Cells; D018118:Chloride Channels / Q000032:analysis / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D004398:Dyneins / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D008297:Male; D008870:Microtubules / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000090007:CLC-2 Chloride Channels; D018118:Chloride Channels; D002712:Chlorides; D004398:Dyneins