A minimal isoform of the TMEM16A protein associated with chloride channel activity.
A minimal isoform of the TMEM16A protein associated with chloride channel activity.
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DOI：
10.1016/j.bbamem.2011.05.017
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发表时间：
2011-09
影响因子：
3.4
通讯作者：
Galietta, Luis J. V.
中科院分区：
文献类型：
--
作者：
Ferrera, Loretta;Scudieri, Paolo;Sondo, Elvira;Caputo, Antonella;Caci, Emanuela;Zegarra-Moran, Olga;Ravazzolo, Roberto;Galietta, Luis J. V.
TMEM16A蛋白，也被称为anoctamin-1，最近被发现是Ca2+激活的Cl -通道的重要组成部分。我们之前报道了通过选择性剪接产生的不同TMEM16A异构体的存在。在目前的研究中，我们已经确定了一个最小的TMEM16A蛋白的功能特性。这种异构体被称为TMEM16A(0)，其氨基末端明显缩短，并且在蛋白质的细胞内区域缺少三个可选片段（总长度：840个氨基酸）。TMEM16A(0)表达与Ca2+激活的Cl -通道活性相关，这是通过基于卤素敏感黄色荧光蛋白、短路电流记录和膜片钳技术的三种不同功能测定来测量的。然而，与TMEM16(abc)（总长度：982个氨基酸）相比，TMEM16A(0)完全缺乏电压依赖性激活。此外，TMEM16A(0)和TMEM16A（abc）对细胞外阴离子替代具有相似但不完全相同的反应，从而表明离子选择性和电导率存在差异。我们的研究结果表明，TMEM16A(0)具有阴离子转运和Ca2+敏感性所需的基本结构域。然而，在更复杂的TMEM16A异构体中存在的替代片段的缺失，改变了通道门控和离子传输能力。►通过功能分析分析了TMEM16A氯离子通道的两种同工异构体。两种同工异构体都被钙离子和运输阴离子激活。较短的同工异构体TMEM16A(0)没有电压依赖性。选择性剪接改变了tmem16a相关离子通道的性质。
TMEM16A protein, also known as anoctamin-1, has been recently identified as an essential component of Ca2+-activated Cl− channels. We previously reported the existence of different TMEM16A isoforms generated by alternative splicing. In the present study, we have determined the functional properties of a minimal TMEM16A protein. This isoform, called TMEM16A(0), has a significantly shortened amino-terminus and lacks three alternative segments localized in the intracellular regions of the protein (total length: 840 amino acids). TMEM16A(0) expression is associated with Ca2+-activated Cl− channel activity as measured by three different functional assays based on the halide-sensitive yellow fluorescent protein, short-circuit current recordings, and patch-clamp technique. However, compared to a longer isoform, TMEM16(abc) (total length: 982 amino acids), TMEM16A(0) completely lacks voltage-dependent activation. Furthermore, TMEM16A(0) and TMEM16A(abc) have similar but not identical responses to extracellular anion replacement, thus suggesting a difference in ion selectivity and conductance. Our results indicate that TMEM16A(0) has the basic domains required for anion transport and Ca2+-sensitivity. However, the absence of alternative segments, which are present in more complex isoforms of TMEM16A, modifies the channel gating and ion transport ability. ► Two isoforms of the TMEM16A chloride channel were analyzed by functional assays. ► Both isoforms are activated by calcium and transport anions. ► The shorter isoform, TMEM16A(0), is devoid of voltage-dependence. ► Alternative splicing modifies the properties of TMEM16A-associated ion channels.
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影响因子：
5.3
作者：
Stoehr, Heidi;Heisig, Julia B.;Schulz, Heidi L.
通讯作者：
Schulz, Heidi L.
影响因子：
4.8
作者：
Ferrera, Loretta;Caputo, Antonella;Galietta, Luis J. V.
通讯作者：
Galietta, Luis J. V.
DOI：
10.1085/jgp.200609507
发表时间：
2006-07
期刊：
The Journal of general physiology
影响因子：
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作者：
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通讯作者：
Greenwood IA
影响因子：
2.4
作者：
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通讯作者：
Arreola, J
影响因子：
64.8
作者：
Yang, Young Duk;Cho, Hawon;Oh, Uhtaek
通讯作者：
Oh, Uhtaek