title: Identification of a dimerization domain in the TMEM16A calcium-activated chloride channel (CaCC).
abstract: Transmembrane proteins with unknown function 16 (TMEM16A) is a calcium-activated chloride channel (CaCC) important for neuronal, exocrine, and smooth muscle functions. TMEM16A belongs to a family of integral membrane proteins that includes another CaCC, TMEM16B, responsible for controlling action potential waveform and synaptic efficacy, and a small-conductance calcium-activated nonselective cation channel, TMEM16F, linked to Scott syndrome. We find that these channels in the TMEM16 family share a homodimeric architecture facilitated by their cytoplasmic N termini. This dimerization domain is important for channel assembly in eukaryotic cells, and the in vitro association of peptides containing the dimerization domain is consistent with a homotypic protein-protein interaction. Amino acid substitutions in the dimerization domain affect functional TMEM16A-CaCC channel expression, as expected from its critical role in channel subunit assembly.
authors.affiliation: Department of Physiology, and Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Tien
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Minor
authors.forename: Yuh Nung
authors.initials: YN
authors.lastname: Jan
authors.forename: Lily Yeh
authors.initials: LY
authors.lastname: Jan
mesh_terms: D000075369:Anoctamin-1; D015153:Blotting, Western; D018118:Chloride Channels / Q000737:chemistry* / Q000235:genetics; D019281:Dimerization; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D008958:Models, Molecular; D005810:Multigene Family / Q000235:genetics*; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D018118:Chloride Channels; D009363:Neoplasm Proteins