Nematode homologue of PQBP1, a mental retardation causative gene, is involved in lipid metabolism.
BACKGROUND
PQBP1 is a causative gene for X-linked mental retardation (MR) whose patients frequently show lean body. C. elegans has a strictly conserved homologue gene of PQBP1, T21D12.3.


RESULTS
We generated Venus-transgenic and T21D12.3-mutant nematodes to analyze developmental expression patterns and in vivo functions of the nematode PQBP1 homologue protein (pqbp-1.1). During development, pqbp-1.1 is expressed from cell proliferation stage to larva stage. In larva, intestinal cells show the highest expression of pqbp-1.1, while it decreases in adult worms. The mutants of pqbp-1.1 show a decrease of the lipid content in intestinal cells. Especially, incorporation of fatty acid into triglyceride is impaired. ShRNA-mediated repression of PQBP1 also leads to reduction of lipid content in mammalian primary white adipocytes. CONCLUSION/ SIGNIFICANCE: These results suggest that pqbp-1.1 is involved in lipid metabolism of intestinal cells. Dysfunction of lipid metabolism might underlie lean body, one of the most frequent symptoms associating with PQBP1-linked MR patients.
Takahashi
Keiko
K
Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Yoshina
Sawako
S
Masashi
Maekawa
M
Ito
Wakana
W
Inoue
Takao
T
Shiwaku
Hiroki
H
Arai
Hiroyuki
H
Mitani
Shohei
S
Okazawa
Hitoshi
H
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D052436:Adipose Tissue, White / Q000166:cytology; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D006801:Humans; D007422:Intestines / Q000166:cytology; D050356:Lipid Metabolism / Q000235:genetics*; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013577:Syndrome
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C119246:PQBP1 protein, human; D011993:Recombinant Fusion Proteins