title: ER E3 ubiquitin ligase HRD-1 and its specific partner chaperone BiP play important roles in ERAD and developmental growth in Caenorhabditis elegans.
abstract: p97 (also called VCP or Cdc48p) and E3 ubiquitin ligases are the key players in retrotranslocation and ubiquitination of substrates in the endoplasmic reticulum-associated degradation (ERAD) pathways. Although their biochemical properties have been well studied, their cellular functions in development have not been revealed. Here, we investigate cellular functions of p97 and E3 ubiquitin ligases in Caenorhabditis elegans as a model organism. We found that C. elegans possesses three E3 ubiquitin ligases (named as HRD-1, HRDL-1 and MARC-6) like mammals, and that their simultaneous depletion caused extremely delayed growth. By monitoring the expression of an ER chaperone gene, it was revealed that p97 and HRD-1 play essential roles in unfolded protein response (UPR) and ERAD pathways. We further found that HRD-1 functions in concert with BiP, and that two BiP paralogues are functionally diversified. HRD-1 and BiP(HSP-3) play important roles in the developmental growth and function of intestinal cells, while HRD-1 and BiP(HSP-4) in the gonad formation. We propose that E3 ubiquitin ligases function in concert with a specific partner chaperone.
authors.affiliation: Division of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Sasagawa
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Teru
authors.initials: T
authors.lastname: Ogura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000502:physiology*; D010641:Phenotype; D010802:Phylogeny; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000074405:Valosin Containing Protein