In Caenorhabditis elegans, the basolateral localization of the Let-23 growt
h factor receptor tyrosine kinase requires the expression of three genes: l
in-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 neu
rons. In this paper, we examine the interaction of these mammalian proteins
in renal epithelia. Coprecipitation experiments demonstrated that mLin-2/C
ASK binds to mLin-7, and immunofluorescent labeling showed that these prote
ins colocalized at the basolateral surface of Madin-Darby canine kidney cel
ls and renal epithelia. Although labeling intensity varied markedly among d
ifferent renal epithelial cells, those cells strongly expressing mLin-7 als
o 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 thi
s region of mLin-7 is also necessary for the targeting of mLin-7 to the bas
olateral surface. Furthermore, the overexpression of mLin-2/CASK mutants in
Madin-Darby canine kidney cells caused endogenous mLin-7 to mislocalize. I
n summary, the NH2 terminus of mLin-7 is crucial for its basolateral locali
zation, likely through its interaction with mLin-2/CASK.