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BMB Rep. 2018 May;51(5):236-241.

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.

Author information

1
College of Pharmacy, CHA University, Sungnam 13488, Korea.
2
Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
3
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea.
4
Department of Physical Education, College of Performing Arts and Sport, Hanyang University, Seoul 04763; Department of Active Aging Industry, Graduate School, Hanyang University, Seoul 04763, Korea.

Abstract

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. [BMB Reports 2018; 51(5): 236-241].

PMID:
29335069
PMCID:
PMC5988578
DOI:
10.5483/bmbrep.2018.51.5.199
[Indexed for MEDLINE]
Free PMC Article

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