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

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.