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Fat storage-inducing transmembrane (FIT or FITM) proteins are related to lipid phosphatase/phosphotransferase enzymes

Hayes, M; Choudhary, V; Ojha, N; Shin, JJ; Han, G-S; Carman, GM; Loewen, CJ; ... Levine, T; + view all (2018) Fat storage-inducing transmembrane (FIT or FITM) proteins are related to lipid phosphatase/phosphotransferase enzymes. Microbial Cell , 5 (2) pp. 88-103. 10.15698/mic2018.02.614. Green open access

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Abstract

Fat storage-inducing transmembrane (FIT or FITM) proteins have been implicated in the partitioning of triacylglycerol to lipid droplets and the budding of lipid droplets from the ER. At the molecular level, the sole relevant interaction is that FITMs directly bind to triacyglycerol and diacylglycerol, but how they function at the molecular level is not known.Saccharomyces cerevisiaehas two FITM homologues: Scs3p and Yft2p. Scs3p was initially identified because deletion leads to inositol auxotrophy, with an unusual sensitivity to addition of choline. This strongly suggests a role for Scs3p in phospholipid biosynthesis. Looking at the FITM family as widely as possible, we found that FITMs are widespread throughout eukaryotes, indicating presence in the last eukaryotic common ancestor. Protein alignments also showed that FITM sequences contain the active site of lipid phosphatase/phosphotransferase (LPT) enzymes. This large family transfers phosphate-containing headgroups either between lipids or in exchange for water. We confirmed the prediction that FITMs are related to LPTs by showing that single amino-acid substitutions in the presumptive catalytic site prevented their ability to rescue growth of the mutants on low inositol/high choline media when over-expressed. The substitutions also prevented rescue of other phenotypes associated with loss of FITM in yeast, including mistargeting of Opi1p, defective ER morphology, and aberrant lipid droplet budding. These results suggest that Scs3p, Yft2p and FITMs in general are LPT enzymes involved in an as yet unknown critical step in phospholipid metabolism.

Type: Article
Title: Fat storage-inducing transmembrane (FIT or FITM) proteins are related to lipid phosphatase/phosphotransferase enzymes
Location: Austria
Open access status: An open access version is available from UCL Discovery
DOI: 10.15698/mic2018.02.614
Publisher version: http://dx.doi.org/10.15698/mic2018.02.614
Language: English
Additional information: Copyright © 2017 Hayes et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/), which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Keywords: endoplasmic reticulum retention motif, endoplasmic reticulum stress, lipid biosynthesis enzyme, lipid droplet, remote homology search, type 2 diabetes
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10044000
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