title: PDLIM5 links kidney anion exchanger 1 (kAE1) to ILK and is required for membrane targeting of kAE1.
abstract: Anion exchanger 1 (AE1) mediates Cl-/HCO3-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.
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK.
authors.forename: Ya
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Hiemstra
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge, UK.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge, UK.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK.
authors.forename: Hannah I
authors.initials: HI
authors.lastname: Karet
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rosen
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK.
authors.forename: Pablo
authors.initials: P
authors.lastname: Moreno
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Karet Frankl
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D002712:Chlorides / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000378:metabolism*; D060588:LIM Domain Proteins / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000235:genetics; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D017693:Sodium Bicarbonate / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001457:Anion Exchange Protein 1, Erythrocyte; D002712:Chlorides; D060588:LIM Domain Proteins; D046912:Multiprotein Complexes; D017346:Protein Serine-Threonine Kinases; D021382:Protein Sorting Signals; D034741:RNA, Small Interfering; D017693:Sodium Bicarbonate; D000099200:Scaffold Protein ILK; C512485:PDLIM5 protein, human