Alternatively spliced C-terminal domains regulate the surface expression of large conductance calcium-activated potassium channels
Alternatively spliced C-terminal domains regulate the surface expression of large conductance calcium-activated potassium channels
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DOI：
10.1016/j.neuroscience.2007.03.038
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发表时间：
2007-06-08
期刊：
影响因子：
3.3
通讯作者：
Dryer, S. E.
中科院分区：
文献类型：
--
作者：
Kim, E. Y.;Ridgway, L. D.;Dryer, S. E.
Slo1 基因，也称为 KCNMA1，编码大电导 Ca2+ 激活的 K+ (BKCa) 通道的成孔亚基。该基因的产物在脊椎动物组织中广泛表达，并存在大量 (>= 20) 的选择性剪接变体，这些变体的门控特性、对调节的敏感性以及向质膜的运输各不相同。大细胞质 C 端的基序对于确定 BKCa 通道的功能特性尤其重要。在这里，我们报道了鸡睫状神经节神经元表达两种 Slo1 剪接变体的转录本和蛋白质，这两种剪接变体在 C 端末端不同。我们将这些变体称为 VEDEC 和 QEDRL（或直系同源哺乳动物版本的 QEERL），以每个亚型中的五个末端氨基酸残基命名。单个睫状神经节神经元优先在不同的亚细胞区室中表达这些变体。此外，在 HEK293T 和 NG108-15 细胞中，QEERL 通道在质膜上的组成型表达水平明显高于 VEDEC 通道。然而，生长因子治疗可以刺激 VEDEC 通道的表面表达达到与 QEERL 相当的水平。此外，我们还发现，由 VEDEC C 端尾残基组成的可溶性蛋白的共表达显着增加了全长 VEDEC 通道的细胞表面表达，表明该区域与导致这些通道保留在细胞内储备中的蛋白质结合。 (C) 2007 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
The Slo1 gene, also known as KCNMA1, encodes the pore-forming subunits of large-conductance Ca2+-activated K+ (BKCa) channels, Products of this gene are widely expressed in vertebrate tissues, and occur in a large number (>= 20) of alternatively spliced variants that vary in their gating properties, susceptibility to modulation, and trafficking to the plasma membrane. Motifs in the large cytoplasmic C-terminal are especially important in determining the functional properties of BKCa channels. Here we report that chick ciliary ganglion neurons express transcripts and proteins of two Slo1 splice variants that differ at the extreme C-terminal. We refer to these variants as VEDEC and QEDRL (or QEERL for the orthologous mammalian versions), after the five terminal amino acid residues in each isoform. Individual ciliary ganglion neurons preferentially express these variants in different subcellular compartments. Moreover, QEERL channels show markedly higher levels of constitutive expression on the plasma membrane than VEDEC channels in HEK293T and NG108-15 cells. However, growth factor treatment can stimulate surface expression of VEDEC channels to levels comparable to those seen with QEERL. In addition, we show that co-expression of a soluble protein composed of VEDEC C-terminal tail residues markedly increases cell surface expression of full-length VEDEC channels, suggesting that this region binds to proteins that cause retention of the these channels in intracellular stores. (C) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.