title: mLin-7 is localized to the basolateral surface of renal epithelia via its NH(2) terminus.
abstract: In Caenorhabditis elegans, the basolateral localization of the Let-23 growth factor receptor tyrosine kinase requires the expression of three genes: lin-2, lin-7, and lin-10. Mammalian homologs of these three genes have been identified, and a complex of their protein products exists in mammalian neurons. In this paper, we examine the interaction of these mammalian proteins in renal epithelia. Coprecipitation experiments demonstrated that mLin-2/CASK binds to mLin-7, and immunofluorescent labeling showed that these proteins colocalized at the basolateral surface of Madin-Darby canine kidney cells and renal epithelia. Although labeling intensity varied markedly among different renal epithelial cells, those cells strongly expressing mLin-7 also showed intense mLin-2/CASK labeling. We have also demonstrated that mLin-2/CASK binding requires amino acids 12-32 of mLin-7 and have shown that this region of mLin-7 is also necessary for the targeting of mLin-7 to the basolateral surface. Furthermore, the overexpression of mLin-2/CASK mutants in Madin-Darby canine kidney cells caused endogenous mLin-7 to mislocalize. In summary, the NH(2) terminus of mLin-7 is crucial for its basolateral localization, likely through its interaction with mLin-2/CASK.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Straight
authors.forename: D
authors.initials: D
authors.lastname: Karnak
authors.forename: J P
authors.initials: JP
authors.lastname: Borg
authors.forename: E
authors.initials: E
authors.lastname: Kamberov
authors.forename: H
authors.initials: H
authors.lastname: Dare
authors.forename: B
authors.initials: B
authors.lastname: Margolis
authors.forename: J B
authors.initials: JB
authors.lastname: Wade
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D004285:Dogs; D004848:Epithelium / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D033921:Vesicular Transport Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C119588:LIN-7 protein, mammalian; C486532:LIN7A protein, human; C486531:LIN7C protein, human; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins