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KMID : 0624620230560030172
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BMB Reports
2023 Volume.56 No. 3 p.172 ~ p.177
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Cytosolic domain regulates the calcium sensitivity and surface expression of BEST1 channels in the HEK293 cells
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Kim Kwon-Woo
Hwang Jun-Mo
Kim Dong-Hyun
Park Hyung-Ju
Lim Hyun-Ho
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Abstract
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BEST family is a class of Ca2+-activated Cl- channels evolutionary well conserved from bacteria to human. The human BEST paralogs (BEST1-BEST4) share significant amino acid sequence homology in the N-terminal region, which forms the transmembrane helicases and contains the direct calcium-binding site, Ca2+-clasp. But the cytosolic C-terminal region is less conserved in the paralogs. Interestingly, this domain-specific sequence conservation is also found in the BEST1 orthologs. However, the functional role of the C-terminal region in the BEST channels is still poorly understood. Thus, we aimed to understand the functional role of the C-terminal region in the human and mouse BEST1 channels by using electrophysiological recordings. We found that the calcium-dependent activation of BEST1 channels can be modulated by the C-terminal region. The C-terminal deletion hBEST1 reduced the Ca2+-dependent current activation and the hBEST1-mBEST1 chimera showed a significantly reduced calcium sensitivity to hBEST1 in the HEK293 cells. And the C-terminal domain could regulate cellular expression and plasma membrane targeting of BEST1 channels. Our results can provide a basis for understanding the C-terminal roles in the structure-function of BEST family proteins.
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KEYWORD
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Bestrophin, Ca2+-dependent activation, Functional modulation, Surface expression, Whole-cell recording
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