Enyedi Agnes, Strehler Emanuel E
Department of Molecular Cell Biology; National Blood Center; Budapest, Hungary.
Commun Integr Biol. 2011 May;4(3):340-3. doi: 10.4161/cib.4.3.15040. Epub 2011 May 1.
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.
质膜钙ATP酶（PMCA）亚型在特定膜区室中的定位对于其在局部钙（Ca2+）处理中的功能至关重要。PMCA2w/b存在于顶端膜中，而选择性剪接变体PMCA2x/b和2z/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NHERF2通过将泵系在其下方的肌动蛋白细胞骨架上，极大地提高了PMCA2w/b在顶端的浓度。这种相互作用需要PMCA2b中的C末端PDZ结合序列，并导致泵的膜保留增加和侧向移动性降低。相比之下，即使NHERF2过表达，PMCA2x/b仍仅位于基底外侧。我们的结果表明，PMCA2中选择性剪接的细胞内环施加了主要的膜靶向信息。NHERF2介导的募集可能是极化细胞调节顶端膜中PMCA2w/b丰度以满足对局部钙（Ca2+）外排增加需求的有效手段。
