Abstract
In C. elegans, the LET-23 receptor tyrosine kinase is localized to the basolateral membranes of polarized vulval epithelial cells. lin-2, lin-7, and lin-10 are required for basolateral localization of LET-23, since LET-23 is mislocalized to the apical membrane in lin-2, lin-7, and lin-10 mutants. Yeast two-hybrid, in vitro binding, and in vivo coimmunoprecipitation experiments show that LIN-2, LIN-7, and LIN-10 form a protein complex. Furthermore, compensatory mutations in lin-7 and let-23 exhibit allele-specific suppression of apical mislocalization and signaling-defective phenotypes. These results present a mechanism for basolateral localization of LET-23 receptor tyrosine kinase by direct binding to the LIN-2/LIN-7/LIN-10 complex. Each of the binding interactions within this complex is conserved, suggesting that this complex may also mediate basolateral localization in mammals.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans Proteins*
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Drosophila
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Epithelial Cells / chemistry
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Epithelial Cells / enzymology
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ErbB Receptors / chemistry
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ErbB Receptors / metabolism*
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Female
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Gene Expression Regulation, Enzymologic
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Helminth Proteins / chemistry
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Helminth Proteins / isolation & purification
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Helminth Proteins / metabolism*
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Mammals
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Membrane Proteins / chemistry
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Membrane Proteins / isolation & purification
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Membrane Proteins / metabolism*
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Multienzyme Complexes / metabolism
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Mutation / physiology
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Precipitin Tests
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Protein Binding / physiology
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Protein Structure, Tertiary
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Proteins*
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Signal Transduction / physiology
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Substrate Specificity
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Vulva / chemistry
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Vulva / cytology
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Vulva / enzymology*
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Yeasts / enzymology
Substances
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Caenorhabditis elegans Proteins
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Helminth Proteins
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LIN-7 protein, C elegans
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Lin-2 protein, C elegans
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Membrane Proteins
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Multienzyme Complexes
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Proteins
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lin-10 protein, C elegans
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ErbB Receptors
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let-23 protein, C elegans