The single pore residue Asp in PKD2L1 determines Ca permeation of the PKD1L3/PKD2L1 complex |
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Authors: | Chisato Fujimoto Yoshiro Ishimaru Yuka Katano Takumi Misaka Tatsuya Yamasoba Tomiko Asakura Keiko Abe |
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Institution: | aDepartment of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan;bDepartment of Oto-Neurotology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu, Tokyo 183-0042, Japan;cDepartment of Otolaryngology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan;dKanagawa Academy of Science and Technology, 3-2-1 Sakado, Takatsu-ku, Kawasaki, Kanagawa 213-0012, Japan |
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Abstract: | The polycystic kidney disease 1-like 3 (PKD1L3)–polycystic kidney disease 2-like 1 (PKD2L1) complex functions as a Ca2+-permeable, non-selective cation channel that is activated by acid and its subsequent removal; this is called an off-response. In this study, we identified a single aspartic residue in PKD2L1 that is responsible for the Ca2+ permeation of the PKD1L3/PKD2L1 complex. Calcium imaging analysis using point mutants of negatively charged amino acids present in the putative pore regions of PKD1L3 and PKD2L1 revealed that neutralization of the aspartic residue in PKD2L1 (D523N), which is conserved among PKD2 family members, abolished Ca2+ permeation, despite robust cell surface expression. In contrast, neutralization of the other negatively charged residues of PKD1L3 (D2049N and E2072Q) and PKD2L1 (D525N and D530N) as well as substitution of Asp523 with a glutamate residue (D523E) had little effect on Ca2+ permeation properties. These results demonstrate that Asp523 in PKD2L1 is a key determinant of Ca2+ permeation into the PKD1L3/PKD2L1 complex and that PKD2L1 contributes to forming the pore of the PKD1L3/PKD2L1 channel. |
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Keywords: | Abbreviations: PKD polycystic kidney disease HEK human embryonic kidney TRP transient receptor potential TM transmembrane |
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