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Nature Research, Scientific Reports, 1(7), 2017

DOI: 10.1038/srep39701

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PDLIM5 links kidney anion exchanger 1 (kAE1) to ILK and is required for membrane targeting of kAE1

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by the Nature Publishing Group. ; Anion exchanger 1 (AE1) mediates Cl$^{-}$/HCO$_{3}$$^{-}$ 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 kidney-AE1 and actin cytoskeleton-associated proteins in polarized cells. ; This work was supported by the Wellcome Trust (grant ref: 088489/Z/09/Z and Strategic award 100140/Z/12/Z to the Cambridge Institute for Medical Research), and the British Heart Foundation (grant ref: SBAG/120). The Addenbrooke's Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre.