Regulation of apical membrane enrichment and retention of plasma membrane Ca ATPase splice variants by the PDZ-domain protein NHERF2.
Regulation of apical membrane enrichment and retention of plasma membrane Ca ATPase splice variants by the PDZ-domain protein NHERF2.
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DOI：
10.4161/cib.4.3.15040
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发表时间：
2011-05-01
影响因子：
--
通讯作者：
Strehler, Emanuel E
中科院分区：
文献类型：
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作者：
Enyedi, Agnes;Strehler, Emanuel E
质膜钙ATP酶（PMCA）异构体在特定的膜室中的定位对于它们在局部Ca（2+）处理中的功能至关重要。PMCA 2 w/B存在于顶膜中，而选择性剪接变体PMCA 2x/B和2 z/B存在于极化上皮细胞的基底外侧膜中。在这里，我们发现，顶端支架蛋白NHERF 2大大提高了顶端浓度的PMCA 2 w/B通过拴泵的底层肌动蛋白细胞骨架。这种相互作用需要PMCA 2b中的C-末端PDZ结合序列，并导致膜保留增加和泵的横向迁移率降低。相比之下，即使NHERF 2过表达，PMCA 2x/B也仅保持在基底外侧。我们的研究结果表明，在PMCA 2的选择性剪接的胞内环强加占主导地位的膜靶向信息。NHERF 2介导的募集可能是极化细胞调节顶膜中PMCA 2 w/B丰度以满足局部Ca（2+）挤出增加的需求的有效手段。
The localization of plasma membrane calcium ATPase (PMCA) isoforms in specified membrane compartments is crucial for their function in local Ca(2+) handling. PMCA2w/b is present in the apical membrane whereas alternative splice variants PMCA2x/b and 2z/b reside in the basolateral membrane in polarized epithelial cells. Here we found that the apical scaffolding protein NHERF2 greatly enhances the apical concentration of PMCA2w/b by tethering the pump to the underlying actin cytoskeleton. The interaction requires the C-terminal PDZ binding sequence in PMCA2b and results in increased membrane retention and decreased lateral mobility of the pump. In contrast, PMCA2x/b remains exclusively basolateral even when NHERF2 is overexpressed. Our results suggest that the alternatively spliced intracellular loop in PMCA2 imposes dominant membrane targeting information. NHERF2-mediated recruitment may be an effective means for polarized cells to regulate the abundance of PMCA2w/b in the apical membrane to meet an increased demand for local Ca(2+) extrusion.