Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK.
Department of Medicine, University of Cambridge, Cambridge, UK.
Sci Rep. 2017 Jan 3;7:39701. doi: 10.1038/srep39701.
Anion exchanger 1 (AE1) mediates Cl/HCO exchange in erythrocytes and kidney intercalated cells where it functions to maintain normal bodily acid-base homeostasis. AE1's C-terminal tail (AE1C) contains multiple potential membrane targeting/retention determinants, including a predicted PDZ binding motif, which are critical for its normal membrane residency. Here we identify PDLIM5 as a direct binding partner for AE1 in human kidney, via PDLIM5's PDZ domain and the PDZ binding motif in AE1C. Kidney AE1 (kAE1), PDLIM5 and integrin-linked kinase (ILK) form a multiprotein complex in which PDLIM5 provides a bridge between ILK and AE1C. Depletion of PDLIM5 resulted in significant reduction in kAE1 at the cell membrane, whereas over-expression of kAE1 was accompanied by increased PDLIM5 levels, underscoring the functional importance of PDLIM5 for proper kAE1 membrane residency, as a crucial linker between kAE1 and actin cytoskeleton-associated proteins in polarized cells.
阴离子交换蛋白 1（AE1）在红细胞和肾脏闰细胞中介导 Cl/HCO 交换，其功能是维持正常的体内酸碱平衡。AE1 的 C 端尾部（AE1C）包含多个潜在的膜靶向/保留决定因素，包括一个预测的 PDZ 结合基序，这对于其正常的膜驻留至关重要。在这里，我们通过 PDLIM5 的 PDZ 结构域和 AE1C 中的 PDZ 结合基序，确定 PDLIM5 是人类肾脏中 AE1 的直接结合伴侣。在这个复合物中，PDLIM5 为 ILK 和 AE1C 之间提供了桥梁。PDLIM5 的耗竭导致细胞膜上 kAE1 的显著减少，而 kAE1 的过表达伴随着 PDLIM5 水平的增加，这强调了 PDLIM5 对于 kAE1 膜驻留的功能重要性，作为极化细胞中 kAE1 和肌动蛋白细胞骨架相关蛋白之间的关键连接物。
