Zerangue N, Schwappach B, Jan Y N, Jan L Y
Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco 94143-0725, USA.
Neuron. 1999 Mar;22(3):537-48. doi: 10.1016/s0896-6273(00)80708-4.
Proper ion channel function often requires specific combinations of pore-forming alpha and regulatory beta subunits, but little is known about the mechanisms that regulate the surface expression of different channel combinations. Our studies of ATP-sensitive K+ channel (K(ATP)) trafficking reveal an essential quality control function for a trafficking motif present in each of the alpha (Kir6.1/2) and beta (SUR1) subunits of the K(ATP) complex. We show that this novel motif for endoplasmic reticulum (ER) retention/retrieval is required at multiple stages of K(ATP) assembly to restrict surface expression to fully assembled and correctly regulated octameric channels. We conclude that exposure of a three amino acid motif (RKR) can explain how assembly of an ion channel complex is coupled to intracellular trafficking.
正常的离子通道功能通常需要形成孔道的α亚基和调节性β亚基的特定组合，但对于调节不同通道组合的表面表达的机制却知之甚少。我们对ATP敏感性钾通道（K(ATP)）转运的研究揭示了K(ATP)复合物的每个α（Kir6.1/2）和β（SUR1）亚基中存在的一个转运基序具有至关重要的质量控制功能。我们表明，这种用于内质网（ER）保留/回收的新基序在K(ATP)组装的多个阶段都是必需的，以将表面表达限制在完全组装且正确调节的八聚体通道上。我们得出结论，一个三氨基酸基序（RKR）的暴露可以解释离子通道复合物的组装如何与细胞内转运相偶联。
