Reference - Detail
|Author||Roudier N, Lefebvre C, Legouis R.|
|Title||CeVPS-27 is an endosomal protein required for the molting and the endocytic trafficking of the low-density lipoprotein receptor-related protein 1 in Caenorhabditis elegans.|
Class E vacuolar protein-sorting (Vps) proteins were first described in yeast as being involved in receptor-mediated endocytosis and multivesicular body formation. Inactivation by RNA interference of the class E VPS genes of the nematode Caenorhabditis elegans revealed heterogeneous phenotypes. We have further characterized the role of the essential gene Cevps-27, ortholog of human hepatocyte growth factor-regulated tyrosine kinase substrate, during the development of C. elegans. Use of green fluorescent protein fusion constructs and antibody staining revealed that Cevps-27 localizes to endosomal membranes. It is widely expressed but enriched in epithelial cells. Cevps-27 mutants presented enlarged endosomal structures and an accumulation of autophagic vesicles as revealed by electron microscopy and the analysis of the autophagic marker LGG-1. Cevps-27 animals arrested at L2-L3 molt with an inability to degrade their old cuticle. This molting phenotype was more severe when Cevps-27 worms were grown on suboptimal concentrations of cholesterol. Furthermore, defective endocytic trafficking of the low-density lipoprotein receptor-related protein 1 (LRP-1) was also observed in Cevps-27 mutants. These results indicate that CeVPS-27 is required for endosomal and autophagic pathways in C. elegans and plays a crucial role in the control of molting through LRP-1 internalization and cholesterol traffic.
|MeSH||Animals Animals, Genetically Modified Autophagy Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Cholesterol Culture Techniques Endosomes / metabolism Gene Expression Regulation, Developmental* Gene Silencing Green Fluorescent Proteins Larva / genetics Larva / physiology Low Density Lipoprotein Receptor-Related Protein-1 / chemistry Low Density Lipoprotein Receptor-Related Protein-1 / metabolism* Microscopy, Confocal Microscopy, Electron Molting Mutation Phenotype Polymerase Chain Reaction Protein Transport RNA / biosynthesis RNA Interference Vesicular Transport Proteins / genetics Vesicular Transport Proteins / physiology*|
|WOS Category||CELL BIOLOGY|
|C.elegans||tm345 tm1483 tm705|