TY - JOUR
T1 - Identification of a dimerization domain in the TMEM16A calcium-activated chloride channel (CaCC)
AU - Tien, Jason
AU - Lee, Hye Young
AU - Minor, Daniel L.
AU - Jan, Yuh Nung
AU - Jan, Lily Yeh
PY - 2013/4/16
Y1 - 2013/4/16
N2 - 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 homodi-meric architecture facilitated by their cytoplasmic N termini. This di-merization domain is important for channel assembly in eukaryotic cells, and the in vitro association of peptides containing the dimer-ization 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.
AB - 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 homodi-meric architecture facilitated by their cytoplasmic N termini. This di-merization domain is important for channel assembly in eukaryotic cells, and the in vitro association of peptides containing the dimer-ization 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.
UR - https://www.scopus.com/pages/publications/84876232419
UR - https://www.scopus.com/pages/publications/84876232419#tab=citedBy
U2 - 10.1073/pnas.1303672110
DO - 10.1073/pnas.1303672110
M3 - Article
C2 - 23576756
AN - SCOPUS:84876232419
SN - 0027-8424
VL - 110
SP - 6352
EP - 6357
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 16
ER -