The LIN-2/LIN-7/LIN-10 complex mediates basolateral membrane localization of the C. elegans EGF receptor LET-23 in vulval epithelial cells.
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.
Kaech
S M
SM
Department of Developmental Biology, Stanford University School of Medicine, California 94305, USA.
Whitfield
C W
CW
Kim
S K
SK
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D004330:Drosophila; D004847:Epithelial Cells / Q000737:chemistry / Q000201:enzymology; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015801:Helminth Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008322:Mammals; D008565:Membrane Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D011506:Proteins; D015398:Signal Transduction / Q000502:physiology; D013379:Substrate Specificity; D014844:Vulva / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D015003:Yeasts / Q000201:enzymology
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C099173:LIN-7 protein, C elegans; C097978:Lin-2 protein, C elegans; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D011506:Proteins; C064105:lin-10 protein, C elegans; D066246:ErbB Receptors; C085873:let-23 protein, C elegans