A C-terminally truncated mouse Best3 splice variant targets and alters the ion balance in lysosome-endosome hybrids and the endoplasmic reticulum.
The Bestrophin family has been characterized as Cl(-) channels in mammals and Na(+) channels in bacteria, but their exact physiological roles remian unknown. In this study, a natural C-terminally truncated variant of mouse Bestrophin 3 (Best3V2) expression in myoblasts and muscles is demonstrated. Unlike full-length Best3, Best3V2 targets the two important intracellular Ca stores: the lysosome and the ER. Heterologous overexpression leads to lysosome swelling and renders it less acidic. Best3V2 overexpression also results in compromised Ca(2+) release from the ER. Knocking down endogenous Best3 expression in myoblasts makes these cells more excitable in response to Ca(2+) mobilizing reagents, such as caffeine. We propose that Best3V2 in myoblasts may work as a tuner to control Ca(2+) release from intracellular Ca(2+) stores.
Department of Animal Sciences and Technology, Qingdao Agricultural University, Qingdao, China.|College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
Lichang
L
Wu
College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
Yu
Y
Sun
College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
Liqiao
L
Ma
College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
Jun
J
Zhu
College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
Baoxia
B
Zhang
Department of Animal Sciences and Technology, Qingdao Agricultural University, Qingdao, China.
Qingjie
Q
Pan
College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
Yuyin
Y
Li
Department of Animal Sciences and Technology, Qingdao Agricultural University, Qingdao, China.
Huanqi
H
Liu
College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
Aipo
A
Diao
Department of Animal Sciences and Technology, Qingdao Agricultural University, Qingdao, China.
Yinchuan
Y
Li
D000818:Animals; D002110:Caffeine / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D007477:Ions / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D017384:Sequence Deletion
D005136:Eye Proteins; D007477:Ions; D020033:Protein Isoforms; C491853:Vmd2L3 protein, mouse; D002110:Caffeine; D002118:Calcium