Olsen Olav, Liu Hui, Wade James B, Merot Jean, Welling Paul A
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Am J Physiol Cell Physiol. 2002 Jan;282(1):C183-95. doi: 10.1152/ajpcell.00249.2001.
The basolateral membrane sorting determinant of an inwardly rectifying potassium channel, Kir 2.3, is comprised of a unique arrangement of trafficking motifs containing tandem, conceivably overlapping, biosynthetic targeting and PDZ-based signals. In the present study, we elucidate a mechanism by which a PDZ interaction coordinates one step in a basolateral membrane sorting program. In contrast to apical missorting of channels lacking the entire sorting domain, deletion of the PDZ binding motif caused channels to accumulate into an endosomal compartment. Here, we identify a new human ortholog of a Caenorhabditis elegans PDZ protein, hLin-7b, that interacts with the COOH-terminal tail of Kir 2.3 in renal epithelia. hLin-7b associates with the channel as a part of a multimeric complex on the basolateral membrane similar to a basolateral membrane complex in C. elegans vulva progenitor cells. Coexpression of hLin-7b with Kir 2.3 dramatically increases channel activity by stabilizing plasma membrane expression. The discovery identifies one component of the sorting machinery and provides evidence for a retention mechanism in a hierarchical basolateral trafficking program.
内向整流钾通道Kir 2.3的基底外侧膜分选决定因素，由包含串联、可能重叠的生物合成靶向信号和基于PDZ的信号的独特排列的转运基序组成。在本研究中，我们阐明了一种机制，通过该机制，PDZ相互作用协调基底外侧膜分选程序中的一个步骤。与缺乏整个分选结构域的通道在顶端的错误分选相反，PDZ结合基序的缺失导致通道积聚在内体区室中。在此，我们鉴定出一种新的与秀丽隐杆线虫PDZ蛋白同源的人类蛋白hLin-7b，它在肾上皮细胞中与Kir 2.3的COOH末端尾巴相互作用。hLin-7b作为基底外侧膜上多聚体复合物的一部分与该通道结合，类似于秀丽隐杆线虫外阴祖细胞中的基底外侧膜复合物。hLin-7b与Kir 2.3共表达通过稳定质膜表达显著增加通道活性。这一发现确定了分选机制的一个组成部分，并为分级基底外侧转运程序中的保留机制提供了证据。
