Functional roles of glutamic acid E143 and E705 residues in the N-terminus and transmembrane domain 7 of Anoctamin 1 in calcium and noxious heat sensing

• Published in: BMB reports Vol. 51; no. 5; pp. 236 - 241
• Main Authors: Choi, Jonghyun, Jang, Yongwoo, Kim, Haedong, Wee, Jungwon, Cho, Sinyoung, Son, Woo Sung, Kim, Sung Min, Yang, Young Duk
• Format: Journal Article
• Language: Korean
• Published: 생화학분자생물학회 31-05-2018
• Subjects: Anoctamin 1; Calcium sensitivity; Heat sensitivity; Ran-dom mutation; Random mutation; Calcium sensitivity; Heat sensitivity; Anoctamin 1
• ISSN: 1976-6696; 1976-670X

Anoctamin 1 (ANO1) is an anion channel that is activated by changes in cytosolic Ca 2＋ concentration and noxious heat. Although the critical roles of ANO1 have been elucidated in various cell types, the control of its gating mechanisms by Ca 2＋ and heat remain more elusive. To investigate critical amino acid residues for modulation of Ca 2＋ and heat sensing, we constructed a randomized mutant library for ANO1. Among 695 random mutants, reduced Ca 2＋ sensitivity was observed in two mutants (mutant 84 and 87). Consequently, the E143A mutant showed reduced sensitivity to Ca 2＋ but not to high temperatures, whereas the E705V mutant exhibited reduced sensitivity to both Ca 2＋ and noxious heat. These results suggest that the glutamic acids (E) at 143 and 705 residues in ANO1 are critical for modulation of Ca 2＋ and/or heat responses. Furthermore, these findings help to provide a better understanding of the Ca 2＋ -mediated activation and heat-sensing mechanism of ANO1. [BMB Reports 2018; 51(5): 236-241]