Reference - Detail
| RRC ID | 6413 |
|---|---|
| Author | Seamen E, Blanchette JM, Han M. |
| Title | P-type ATPase TAT-2 negatively regulates monomethyl branched-chain fatty acid mediated function in post-embryonic growth and development in C. elegans. |
| Journal | 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. |
| Volume | 5(8) |
| Pages | e1000589 |
| Published | 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 |
| Times Cited | 24 |
| WOS Category | GENETICS & HEREDITY |
| Altmetric score |
オルトメトリクス指標項目
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| Total number of mentions | 0 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm2332 tm1034 tm1275 tm1801 tm1955 tm1773 |