Basolateral localization of the Caenorhabditis elegans epidermal growth factor receptor in epithelial cells by the PDZ protein LIN-10.
In Caenorhabditis elegans, the EGF receptor (encoded by let-23) is localized to the basolateral membrane domain of the epithelial vulval precursor cells, where it acts through a conserved Ras/MAP kinase signaling pathway to induce vulval differentiation. lin-10 acts in LET-23 receptor tyrosine kinase basolateral localization, because lin-10 mutations result in mislocalization of LET-23 to the apical membrane domain and cause a signaling defective (vulvaless) phenotype. We demonstrate that the previous molecular identification of lin-10 was incorrect, and we identify a new gene corresponding to the lin-10 genetic locus. lin-10 encodes a protein with regions of similarity to mammalian X11/mint proteins, containing a phosphotyrosine-binding and two PDZ domains. A nonsense lin-10 allele that truncates both PDZ domains only partially reduces lin-10 gene activity, suggesting that these protein interaction domains are not essential for LIN-10 function in vulval induction. Immunocytochemical experiments show that LIN-10 is expressed in vulval epithelial cells and in neurons. LIN-10 is present at low levels in the cytoplasm and at the plasma membrane and at high levels at or near the Golgi. LIN-10 may function in secretion of LET-23 to the basolateral membrane domain, or it may be involved in tethering LET-23 at the basolateral plasma membrane once it is secreted.
Whitfield
C W
CW
Department of Developmental Biology, Stanford University Medical Center, Stanford, California 94305, USA.
Bénard
C
C
Barnes
T
T
Hekimi
S
S
Kim
S K
SK
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D004847:Epithelial Cells / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism*; D007814:Larva / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D011506:Proteins; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; C064105:lin-10 protein, C elegans; D066246:ErbB Receptors; C085873:let-23 protein, C elegans