Ca2+-dependent phospholipid scrambling by a reconstituted TMEM16 ion channel.
Ca2+-dependent phospholipid scrambling by a reconstituted TMEM16 ion channel.
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DOI：
10.1038/ncomms3367
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发表时间：
2013
影响因子：
16.6
通讯作者：
Accardi A
中科院分区：
文献类型：
--
作者：
Malvezzi M;Chalat M;Janjusevic R;Picollo A;Terashima H;Menon AK;Accardi A
磷脂乱序酶破坏质膜的脂质不对称性，使磷脂酰丝氨酸外化以触发血液凝固并标记凋亡细胞。最近，TMEM 16家族的Ca 2+门控通道的成员已被证明参与Ca 2+依赖性扰乱。然而，它们是加扰还是调节加扰的信道是有争议的。在这里，我们表明，纯化的afTMEM 16，从烟曲霉，是一种双功能蛋白：它是一个Ca 2+门控通道，与其他TMEM 16同系物的特点，和Ca 2+依赖的乱序酶，与哺乳动物磷脂乱序酶的预期特性。值得注意的是，我们发现，一个单一的Ca 2+网站调节离子和脂质单独的跨膜途径。另外两个纯化的TMEM 16通道同源物不介导加扰，表明该家族分化为通道和通道/加扰酶。我们建议，离子和脂质途径的空间分离的基础上的TMEM 16家族的进化分歧，和其他同系物，如TMEM 16 F，也可能是双功能通道/扰码。
Phospholipid scramblases disrupt the lipid asymmetry of the plasma membrane, externalizing phosphatidylserine to trigger blood coagulation and mark apoptotic cells. Recently, members of the TMEM16 family of Ca2+-gated channels have been shown to be involved in Ca2+-dependent scrambling. It is however controversial whether they are scramblases or channels regulating scrambling. Here we show that purified afTMEM16, from Aspergillus fumigatus, is a dual-function protein: it is a Ca2+-gated channel, with characteristics of other TMEM16 homologues, and a Ca2+-dependent scramblase, with the expected properties of mammalian phospholipid scramblases. Remarkably, we find that a single Ca2+ site regulates separate transmembrane pathways for ions and lipids. Two other purified TMEM16-channel homologues do not mediate scrambling, suggesting that the family diverged into channels and channel/scramblases. We propose that the spatial separation of the ion and lipid pathways underlies the evolutionary divergence of the TMEM16 family, and that other homologues, such as TMEM16F, might also be dual-function channel/scramblases.
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影响因子：
5.6
作者：
Lee, Seok-Yong;Letts, James A.;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
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作者：
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作者：
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Ferrera, Loretta;Scudieri, Paolo;Sondo, Elvira;Caputo, Antonella;Caci, Emanuela;Zegarra-Moran, Olga;Ravazzolo, Roberto;Galietta, Luis J. V.
通讯作者：
Galietta, Luis J. V.
影响因子：
4.8
作者：
Sheridan, John T.;Worthington, Erin N.;Tarran, Robert
通讯作者：
Tarran, Robert