P-type ATPase, TAT-2, negatively regulates monomethyl branched-chain fatty acid mediated function in post-embryonic growth and development in Caenorhabditis elegans [electronic resource]
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| Online Access: |
Online Access |
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| Main Author: | |
| Other Authors: | , |
| Format: | Thesis Electronic eBook |
| Language: | English |
| Published: |
2009.
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| Abstract: | C. elegans provide an excellent model system to understand fatty acid and lipid homeostasis at an organismal level. By combining manipulation of genetics and biochemical techniques, progress can be made relatively quickly in this simple system. In particular, previously under-studied fatty acids, monomethyl branched-chain fatty acids (mmBCFAs) are essential for C. elegans growth and development. This provides a unique opportunity to make novel discoveries about the role of mmBCFAs in C. elegans, which also may be conserved in other organisms and other fatty acid metabolic processes. 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 downstream 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 membrane asymmetry and the critical regulatory function of a specific fatty acid. |
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| Item Description: | Source: Dissertation Abstracts International, Volume: 70-07, Section: B, page: 3948. Advisers: Min Han; Andrew Staehelin. |
| Physical Description: | 95 pages. |
| ISBN: | 9781109281842 |