Dynamic regulation of β1 subunit trafficking controls vascular contractility
Dynamic regulation of β1 subunit trafficking controls vascular contractility
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DOI：
10.1073/pnas.1317527111
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发表时间：
2014-02-11
影响因子：
11.1
通讯作者：
Jaggar, Jonathan H.
中科院分区：
文献类型：
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作者：
Leo, M. Dennis;Bannister, John P.;Jaggar, Jonathan H.
由成孔亚基和辅助亚基组成的离子通道控制几乎所有细胞类型的生理功能。传统观点认为，通道在蛋白复合物的顺行质膜运输之前与其辅助亚基组装。表面通道的多亚基组合物是否在蛋白质合成后固定或灵活并对急性和潜在的快速调节开放以控制活性和细胞兴奋性尚不清楚。动脉平滑肌细胞（肌细胞）表达大电导Ca2+激活钾（BK）通道α和辅助β 1亚基，它们是动脉收缩性的功能性重要调节剂。在这里，我们表明，天然BK α亚基主要（类似于95%）质膜定位于人类和大鼠动脉肌细胞。相比之下，只有一小部分（约10%）的总β 1亚基位于细胞表面。免疫荧光共振能量转移显微镜显示细胞内β 1亚基储存在Rab11A阳性再循环内体中。一氧化氮（NO），通过cGMP依赖性蛋白激酶和cAMP依赖性途径作用，刺激快速（
Ion channels composed of pore-forming and auxiliary subunits control physiological functions in virtually all cell types. A conventional view is that channels assemble with their auxiliary subunits before anterograde plasma membrane trafficking of the protein complex. Whether the multisubunit composition of surface channels is fixed following protein synthesis or flexible and open to acute and, potentially, rapid modulation to control activity and cellular excitability is unclear. Arterial smooth muscle cells (myocytes) express large-conductance Ca2+-activated potassium (BK) channel alpha and auxiliary beta 1 subunits that are functionally significant modulators of arterial contractility. Here, we show that native BK alpha subunits are primarily (similar to 95%) plasma membrane-localized in human and rat arterial myocytes. In contrast, only a small fraction (similar to 10%) of total beta 1 subunits are located at the cell surface. Immunofluorescence resonance energy transfer microscopy demonstrated that intracellular beta 1 subunits are stored within Rab11A-postive recycling endosomes. Nitric oxide (NO), acting via cGMP-dependent protein kinase, and cAMP-dependent pathways stimulated rapid (