Interaction between the transcriptional corepressor Sin3B and voltage-gated sodium channels modulates functional channel expression
Por:
Vega A.V., Avila G., Matthews G.
Publicada:
30 sep 2013
Categoría:
Multidisciplinary
Resumen:
Proteins that interact with voltage-gated sodium (Na-v) channels are important in channel sorting and modulation. In this study, we identified the transcriptional regulator, Sin3B, as a novel binding partner of Na-v channels in a yeast two-hybrid screen and confirmed the interaction using pull-down assays, co-immunoprecipitation, and immunofluorescence-colocalization. Because both long (similar to 1100-residue) and short (N-terminal 293 residues) Sin3B variants interacted with Na-v channels, binding occurred within the N-terminal region containing two paired-amphipathic helix domains. In Na-v 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 Na-v-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 channel
Filiaciones:
Vega A.V.:
UNAM Reyes Iztacala Edo, Carrera Med Cirujano UBIMED FES Iztacala, Mex 54090, Mexico
Avila G.:
Department of Biochemistry, Cinvestav-IPN AP 14-740, Mexico City, DF 07000, Mexico
Matthews G.:
Department of Neurobiology and Behavior, Centers for Molecular Medicine, Stony Brook University, Stony Brook, NY 11794-5230, United States
Gold
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