CHE-14, a protein with a sterol-sensing domain, is required for apical sorting in C. elegans ectodermal epithelial cells

Curr Biol. 2000 Sep 21;10(18):1098-107. doi: 10.1016/s0960-9822(00)00695-3.


Background: Polarised trafficking of proteins is critical for normal expression of the epithelial phenotype, but its genetic control is not understood. The regulatory gene lin-26 is essential for normal epithelial differentiation in the nematode Caenorhabditis elegans. To identify potential effectors of lin-26, we characterised mutations that result in lin-26-like phenotypes. Here, we report the phenotypic and molecular analysis of one such mutant line, che-14.

Results: Mutations in che-14 resulted in several partially penetrant phenotypes affecting the function of most epithelial or epithelial-like cells of the ectoderm, including the hypodermis, excretory canal, vulva, rectum and several support cells. The defects were generally linked to the accumulation of vesicles or amorphous material near the apical surface, suggesting that secretion was defective. The CHE-14 protein showed similarity to proteins containing sterol-sensing domains, including Dispatched, Patched and NPC1. A fusion protein between full-length CHE-14 and the green fluorescent protein became localised to the apical surface of epithelial cells that require che-14 function. Deletions that removed the predicted transmembrane domains or extracellular loops of CHE-14 abolished apical localisation and function of the protein.

Conclusions: We propose that CHE-14 is involved in a novel secretory pathway dedicated to the exocytosis of lipid-modified proteins at the apical surface of certain epithelial cells. Our data raise the possibility that the primordial function of proteins containing a sterol-sensing domain is to control vesicle trafficking: CHE-14 and Dispatched in exocytosis, Patched and NPC1 in endocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs*
  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans / ultrastructure
  • Caenorhabditis elegans Proteins*
  • Cell Polarity
  • Cytoplasmic Vesicles / metabolism
  • Cytoplasmic Vesicles / ultrastructure
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Ectoderm / cytology*
  • Ectoderm / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Exocytosis
  • Helminth Proteins / chemistry
  • Helminth Proteins / genetics*
  • Helminth Proteins / physiology*
  • Microscopy, Electron
  • Microscopy, Phase-Contrast
  • Neurons / cytology
  • Neurons / ultrastructure
  • Phenotype
  • Plasmids / genetics
  • Protein Transport*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Deletion / genetics
  • Sterols / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / physiology


  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Helminth Proteins
  • Recombinant Fusion Proteins
  • Sterols
  • Transcription Factors
  • lin-26 protein, C elegans