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KMID : 0624620180510050236
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BMB Reports
2018 Volume.51 No. 5 p.236 ~ p.241
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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
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Choi Jong-Hyun
Jang Yong-Woo
Kim Hae-Dong
Wee Jung-Won
Cho Sin-Young
Son Woo-Sung
Kim Sung-Min
Yang Young-Duk
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Abstract
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Anoctamin 1 (ANO1) is an anion channel that is activated by changes in cytosolic Ca2+ concentration and noxious heat. Although the critical roles of ANO1 have been elucidated in various cell types, the control of its gating mechanisms by Ca2+ and heat remain more elusive. To investigate critical amino acid residues for modulation of Ca2+ and heat sensing, we constructed a randomized mutant library for ANO1. Among 695 random mutants, reduced Ca2+ sensitivity was observed in two mutants (mutant 84 and 87). Consequently, the E143A mutant showed reduced sensitivity to Ca2+ but not to high temperatures, whereas the E705V mutant exhibited reduced sensitivity to both Ca2+ and noxious heat. These results suggest that the glutamic acids (E) at 143 and 705 residues in ANO1 are critical for modulation of Ca2+ and/or heat responses. Furthermore, these findings help to provide a better understanding of the Ca2+-mediated activation and heat-sensing mechanism of ANO1.
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KEYWORD
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Anoctamin 1, Calcium sensitivity, Heat sensitivity, Random mutation
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