RRC ID 6413
著者 Seamen E, Blanchette JM, Han M.
タイトル P-type ATPase TAT-2 negatively regulates monomethyl branched-chain fatty acid mediated function in post-embryonic growth and development in C. elegans.
ジャーナル PLoS Genet
Abstract Monomethyl branched-chain fatty acids (mmBCFAs) are essential for Caenorhabditis elegans growth and development. To identify factors acting downstream of mmBCFAs for their function in growth regulation, we conducted a genetic screen for suppressors of the L1 arrest that occurs in animals depleted of the 17-carbon mmBCFA C17ISO. Three of the suppressor mutations defined an unexpected player, the P-type ATPase TAT-2, which belongs to the flippase family of proteins that are implicated in mediating phospholipid bilayer asymmetry. We provide evidence that TAT-2, but not other TAT genes, has a specific role in antagonizing the regulatory activity of mmBCFAs in intestinal cells. Interestingly, we found that mutations in tat-2 also suppress the lethality caused by inhibition of the first step in sphingolipid biosynthesis. We further showed that the fatty acid side-chains of glycosylceramides contain 20%-30% mmBCFAs and that this fraction is greatly diminished in the absence of mmBCFA biosynthesis. These results suggest a model in which a C17ISO-containing sphingolipid may mediate the regulatory functions of mmBCFAs and is negatively regulated by TAT-2 in intestinal cells. This work indicates a novel connection between a P-type ATPase and the critical regulatory function of a specific fatty acid.
巻・号 5(8)
ページ e1000589
公開日 2009-8-1
DOI 10.1371/journal.pgen.1000589
PMID 19662161
PMC PMC2716530
MeSH Amino Acid Sequence Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Down-Regulation* Fatty Acids / chemistry* Fatty Acids / metabolism* Gene Expression Regulation, Developmental Intestinal Mucosa / metabolism Intestines / chemistry Intestines / enzymology Molecular Sequence Data Mutation Phospholipid Transfer Proteins / chemistry Phospholipid Transfer Proteins / genetics Phospholipid Transfer Proteins / metabolism* Sequence Alignment
IF 5.175
引用数 24
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm2332 tm1034 tm1275 tm1801 tm1955 tm1773