RRC ID 47233
Author Wakabayashi S, Sawamura N, Voelzmann A, Broemer M, Asahi T, Hoch M.
Title Ohgata, the Single Drosophila Ortholog of Human Cereblon, Regulates Insulin Signaling-dependent Organismic Growth.
Journal J. Biol. Chem.
Abstract Cereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex that is highly conserved in animals and plants. CRBN proteins have been implicated in various biological processes such as development, metabolism, learning, and memory formation, and their impairment has been linked to autosomal recessive non-syndromic intellectual disability and cancer. Furthermore, human CRBN was identified as the primary target of thalidomide teratogenicity. Data on functional analysis of CRBN family members in vivo, however, are still scarce. Here we identify Ohgata (OHGT), the Drosophila ortholog of CRBN, as a regulator of insulin signaling-mediated growth. Using ohgt mutants that we generated by targeted mutagenesis, we show that its loss results in increased body weight and organ size without changes of the body proportions. We demonstrate that ohgt knockdown in the fat body, an organ analogous to mammalian liver and adipose tissue, phenocopies the growth phenotypes. We further show that overgrowth is due to an elevation of insulin signaling in ohgt mutants and to the down-regulation of inhibitory cofactors of circulating Drosophila insulin-like peptides (DILPs), named acid-labile subunit and imaginal morphogenesis protein-late 2. The two inhibitory proteins were previously shown to be components of a heterotrimeric complex with growth-promoting DILP2 and DILP5. Our study reveals OHGT as a novel regulator of insulin-dependent organismic growth in Drosophila.
Volume 291(48)
Pages 25120-25132
Published 2016-11-25
DOI 10.1074/jbc.M116.757823
PII M116.757823
PMID 27702999
PMC PMC5122779
MeSH Animals Cell Line Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster Gene Knockdown Techniques Humans Insulins* / genetics Insulins* / metabolism Peptide Hydrolases / genetics Peptide Hydrolases / metabolism Signal Transduction / physiology*
IF 4.011
Times Cited 0
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Drosophila 3925R-3