C-Terminal Membrane Association of Bestrophin 3 and Its Activation as a Chloride Channel
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- 作者：Xiaohua Han (1)
Zhiqiang Qu (1) (2)
Junxia Xie (1)
Hong Jiang (1) - 关键词：Chloride channel ; Bestrophin 3 ; Channel activation ; C terminus ; Membrane association
- 刊名：Journal of Membrane Biology
- 出版年：2013
- 出版时间：February 2013
- 年：2013
- 卷：246
- 期：2
- 页码：177-182
- 全文大小：289KB
- 参考文献：1. Broegger T, Jacobsen JC, Secher Dam V, Boedtkjer DM, Kold-Petersen H, Pedersen FS et al (2011) Bestrophin is important for the rhythmic but not the tonic contraction in rat mesenteric small arteries. Cardiovasc Res 91(4):685-93
2. Kong D, Yamori T (2009) Advances in development of phosphatidylinositol 3-kinase inhibitors. Curr Med Chem 16:2839-854 10.2174/092986709788803222">CrossRef
3. Large WA, Wang Q (1996) Characteristics and physiological role of the Ca2+-activate Cl?/sup> conductance in smooth muscle. Am J Physiol Cell Physiol 271:C435–C454
4. Matchkov VV, Larsen P, Bouzinova EV, Rojek A, Boedtkjer DM, Golubinskaya V et al (2008) Bestrophin-3 (vitelliform macular dystrophy 2-like 3 protein) is essential for the cGMP-dependent calcium-activated chloride conductance in vascular smooth muscle cells. Circ Res 103:864-72 10.1161/CIRCRESAHA.108.178517">CrossRef
5. O’Driscoll KE, Hatton WJ, Burkin HR, Leblanc N, Britton FC (2008) Expression, localization, and functional properties of Bestrophin 3 channel isolated from mouse heart. Am J Physiol Cell Physiol 295:C1610–C1624 10.1152/ajpcell.00461.2008">CrossRef
6. Qu Z, Cui Y, Hartzell HC (2006) A short motif in the C terminus of mouse bestrophin 3 inhibits its activation as a Cl channel. FEBS Lett 580:2141-146 10.1016/j.febslet.2006.03.025">CrossRef
7. Qu Z, Yu K, Cui Y, Ying C, Hartzell C (2007) Activation of bestrophin Cl?/sup> channels is regulated by C-terminal domains. J Biol Chem 282:17460-7467 10.1074/jbc.M701043200">CrossRef
8. Qu Z, Han X, Cui Y, Li C (2010) A PI3 kinase inhibitor found to activate bestrophin 3. J Cardiovasc Pharmacol 55:110-15 10.1097/FJC.0b013e3181c87c85">CrossRef
9. Tsunenari T, Sun H, Williams J, Cahill H, Smallwood P, Yau KW et al (2003) Structure–function analysis of the bestrophin family of anion channels. J Biol Chem 278:41114-1125 10.1074/jbc.M306150200">CrossRef - 作者单位：Xiaohua Han (1)
Zhiqiang Qu (1) (2)
Junxia Xie (1)
Hong Jiang (1)
1. Department of Physiology, Qingdao University Medical College, Qingdao, 266071, People’s Republic of China
2. Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA - ISSN：1432-1424
文摘
Bestrophin 3 (Best3), a member of the bestrophin Cl?/sup> channel family, is a candidate of cGMP-sensitive, Ca2+-activated Cl?/sup> channel in vascular smooth muscle cells. The Best3 channel was recently found to play an important role in vasomotion. However, the mechanism for its activation has not been clarified. In previous studies, we found that a Best3 C-terminal sequence (amino acids 353-04) was associated with the cellular membrane. The sequence includes an autoinhibitory domain (356IPSFLGS362) and a downstream basic residue domain (amino acids 384-97). In this study, we found that the sequence (368-83) between the two domains is actually a determinant for Best3 C-terminal membrane associability. Deletion of the sequence almost abolished the membrane association but did not activate the Best3 channel. Treatment of Best3-expressing HEK293 cells with the PI3Kα inhibitor IV (a Best3 activator) could not abolish but weakened the Best3 membrane association. The result supports the assumption that the positively charged basic residues in the Best3 C terminus are likely associated with the membranous negatively charged phospholipids, which plays a role in the regulation of Best3 activation. But the relationship between membrane associability and Best3 activation seems more complicated than expected.