Abstract
Proteins that interact with voltage-gated sodium (Nav) channels are important in channel sorting and modulation. In this study, we identified the transcriptional regulator, Sin3B, as a novel binding partner of Nav channels in a yeast two-hybrid screen and confirmed the interaction using pull-down assays, co-immunoprecipitation, and immunofluorescence-colocalization. Because both long (~1100-residue) and short (N-terminal 293 residues) Sin3B variants interacted with Nav channels, binding occurred within the N-terminal region containing two paired-amphipathic helix domains. In Nav channels, Sin3B bound to a 132-residue portion of the cytoplasmic C-terminus. Expression of the short Sin3B variant strongly reduced native sodium current and Nav-channel gating charge in the neuronal cell line N1E-115, without affecting the voltage-dependence of activation. Because the total amount of channel protein was unchanged by Sin3B, binding of Sin3B likely decreases the number of channels in the plasma membrane, suggesting that interaction with Sin3B influences Nav-channel trafficking or stability in the membrane.
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