title: Differential localization of mammalian Lin-7 (MALS/Veli) PDZ proteins in the kidney.
abstract: 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 mammalian Lin-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 TAL and distal segments appear to have the most significant capacity for a basolateral membrane-targeting mechanism involving different MALS/Veli isoforms.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Olav
authors.initials: O
authors.lastname: Olsen
authors.forename: James B
authors.initials: JB
authors.lastname: Wade
authors.forename: Nick
authors.initials: N
authors.lastname: Morin
authors.forename: David S
authors.initials: DS
authors.lastname: Bredt
authors.forename: Paul A
authors.initials: PA
authors.lastname: Welling
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D005455:Fluorescent Antibody Technique; D007685:Kidney Tubules, Collecting / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D009399:Nephrons / Q000502:physiology; D020033:Protein Isoforms; D051381:Rats; D017207:Rats, Sprague-Dawley; D033921:Vesicular Transport Proteins
chemical_list: D000911:Antibodies, Monoclonal; C486532:LIN7A protein, human; D008565:Membrane Proteins; D020033:Protein Isoforms; D033921:Vesicular Transport Proteins