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Article
Nature Neuroscience  8, 435 - 442 (2005)
Published online: 13 March 2005; | doi:10.1038/nn1418

A tctex1-Ca2+ channel complex for selective surface expression of Ca2+ channels in neurons

Meizan Lai1, 5, Fushun Wang5, Joyce G Rohan2, Yuka Maeno-Hikichi1, 5, Yuan Chen1, 5, Yi Zhou3, Guangping Gao4, William A Sather2 & Ji-fang Zhang1, 5

1  Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA.

2  Department of Pharmacology, University of Colorado Health Sciences Center, P.O. Box 6511, Aurora, Colorado 80045, USA.

3  Department of Neurobiology, University of Alabama at Birmingham, 1719 6th Avenue South, Birmingham, Alabama 35294, USA.

4  Department of Molecular & Cellular Engineering, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA.

5  Current addresses: Department of Physiology, Jefferson Medical College, 1020 Locust Street, Philadelphia, Pennsylvania 19107, USA (M.L., F.W., Y.C. and J.-f.Z.); Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA (Y.M.-H.).

Correspondence should be addressed to Ji-fang Zhang Ji-fang.Zhang@Jefferson.edu
Voltage-gated Ca2+ channels (VGCCs) are important in regulating a variety of cellular functions in neurons. It remains poorly understood how VGCCs with different functions are sorted within neurons. Here we show that the t-complex testis-expressed 1 (tctex1) protein, a light-chain subunit of the dynein motor complex, interacts directly and selectively with N- and P/Q-type Ca2+ channels, but not L-type Ca2+ channels. The interaction is insensitive to Ca2+. Overexpression in hippocampal neurons of a channel fragment containing the binding domain for tctex1 significantly decreases the surface expression of endogenous N- and P/Q-type Ca2+ channels but not L-type Ca2+ channels, as determined by immunostaining. Furthermore, disruption of the tctex1−Ca2+ channel interaction significantly reduces the Ca2+ current density in hippocampal neurons. These results underscore the importance of the specific tctex1-channel interaction in determining sorting and trafficking of neuronal Ca2+ channels with different functionalities.

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Nature Neuroscience
ISSN: 1097-6256
EISSN: 1546-1726
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