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1 Department of Physiology, University of Maryland, School of Medicine, Baltimore, MD, USA; Department of Physiology, University of California San Francisco Medical School, San Francisco, CA, USA
* To whom correspondence should be addressed. E-mail: pwelling{at}umaryland.edu.
Lin 7 PDZ proteins, also called MALS or Velis, have been shown to coordinate basolateral membrane expression of various target proteins in renal epithelial cell models. Three different Lin 7/MALS/Veli isoforms, encoded by separate genes, have been identified. Here we show that each Lin 7/MALS/Veli isoform is expressed in the kidney. Using MALS isoform specific antibodies in combination with cell-specific marker antibodies, we found the products of the three mLin-7/MALS/Veli genes are differentially expressed along the length of the nephron. MALS/Veli 1 is predominately expressed in the glomerulus, thick ascending limb of Henle's loop (TAL), and the distal convoluted tubule (DCT). MALS/Veli 2 is exclusively expressed in the vasa recta. MALS/Veli 3 is largely located in the DCT and collecting duct. The subcellular localization of MALS/Veli proteins can vary, depending on the isoform and the cell-type. In contrast to the predominate basolateral location of MALS/Veli 1 in the TAL and DCT and MALS/Veli 3 in the DCT, MALS/Veli 1 is found diffusely throughout the cytosol of intercalated cells. In the collecting duct, MALS/Veli 3 is chiefly located on the basal membrane. Collectively, these results suggest that different MALS/Veli isoforms may carry out cell-type specific functions. The thick ascending limb and distal segments appear to have most significant capacity for a basolateral membrane targeting mechanism involving different MALS/Veli isoforms.
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