Qu Zhiqiang, Cui Yuanyuan, Hartzell Criss
Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, 615 Michael Street, 535 Whitehead Building, Atlanta, GA 30322-3030, USA.
FEBS Lett. 2006 Apr 3;580(8):2141-6. doi: 10.1016/j.febslet.2006.03.025. Epub 2006 Mar 20.
Bestrophins are a new family of anion channels. Here, we examined the Cl channel activity of mBest4. Surprisingly, wild type mouse bestrophin-4 (mBest4) did not induce functional Cl channels when over-expressed in HEK293 cells. However, deletion of part of the C-terminus (residues 353-669) produced large Cl currents, suggesting the presence of a C-terminal motif that inhibited Cl channel function. Deletion of a short motif (356-364) or substitution of certain residues in this motif with alanines also resulted in expression of robust Cl currents. The channel activity of the mBest4 protein lacking the C-terminus (residues 353-669) was specifically inhibited by co-expression of C-terminal fragments of mBest4 having the inhibitory motif, suggesting that the C-terminal motif blocked mBest4 channel activity probably by interacting with the channel pore.
贝斯特罗芬家族是一类新的阴离子通道。在此，我们检测了小鼠贝斯特罗芬4（mBest4）的氯离子通道活性。令人惊讶的是，野生型小鼠贝斯特罗芬4（mBest4）在HEK293细胞中过表达时并未诱导出功能性氯离子通道。然而，缺失部分C末端（353 - 669位氨基酸残基）会产生较大的氯离子电流，这表明存在一个抑制氯离子通道功能的C末端基序。缺失一个短基序（356 - 364位氨基酸残基）或用丙氨酸替换该基序中的某些残基也会导致大量氯离子电流的表达。缺少C末端（353 - 669位氨基酸残基）的mBest4蛋白的通道活性会被具有抑制性基序的mBest4 C末端片段的共表达特异性抑制，这表明C末端基序可能通过与通道孔相互作用来阻断mBest4通道活性。
