Linked Life Data

12837764

Source:http://linkedlifedata.com/resource/pubmed/id/12837764

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
38
pubmed:dateCreated
2003-9-15
pubmed:abstractText
Mammalian enzymes in late cholesterol biosynthesis have been localized uniformly over the endoplasmic reticulum by enzymatic methods. We report here the first mammalian cholesterol biosynthetic enzyme unequivocally localized at the surface of intracellular lipid storage droplets. NAD(P)H steroid dehydrogenase-like protein (Nsdhl), a mammalian C-3 sterol dehydrogenase involved in the conversion of lanosterol into cholesterol, was localized on lipid droplets by immunofluorescence microscopy and subcellular fractionation. Nsdhl was localized on lipid droplets even when cell growth exclusively depended on cholesterol biosynthesis mediated by this enzyme. Depletion of fatty acids in culture medium reduced the development of lipid droplets and caused Nsdhl redistribution to the endoplasmic reticulum. Elevating oleic acid in medium induced well developed, Nsdhl-positive lipid droplets, and simultaneously caused a reduction in cellular conversion of lanosterol into cholesterol. Manipulated human NSDHL with a missense mutation (G205S) causing a human embryonic developmental disorder, congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome, could no longer be localized on lipid droplets. Although the expression of wild-type NSDHL could restore the defective growth of a CHO cholesterol auxotroph, LEX2 in cholesterol-deficient medium, the expression of NSDHL(G205S) failed to do so. These results point to functional significance of the localization of Nsdhl on lipid droplets. Functional significance was also suggested by the colocalization of Nsdhl on lipid droplets with TIP47, a cargo selection protein for mannose 6-phosphate receptors from late endosomes to the trans-Golgi network. These results add to the growing notion that the lipid droplet is an organelle endowed with more complex roles in various biological phenomena.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
36819-29
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12837764-3-Hydroxysteroid Dehydrogenases, pubmed-meshheading:12837764-Animals, pubmed-meshheading:12837764-CHO Cells, pubmed-meshheading:12837764-Cholesterol, pubmed-meshheading:12837764-Chromatography, Thin Layer, pubmed-meshheading:12837764-Cricetinae, pubmed-meshheading:12837764-DNA, Complementary, pubmed-meshheading:12837764-Endoplasmic Reticulum, pubmed-meshheading:12837764-Fatty Acids, pubmed-meshheading:12837764-HeLa Cells, pubmed-meshheading:12837764-Humans, pubmed-meshheading:12837764-Hydroxysteroid Dehydrogenases, pubmed-meshheading:12837764-Lipid Metabolism, pubmed-meshheading:12837764-Microscopy, Fluorescence, pubmed-meshheading:12837764-Models, Chemical, pubmed-meshheading:12837764-Mutation, pubmed-meshheading:12837764-Mutation, Missense, pubmed-meshheading:12837764-NADPH Dehydrogenase, pubmed-meshheading:12837764-Peptides, pubmed-meshheading:12837764-Sterols, pubmed-meshheading:12837764-Subcellular Fractions, pubmed-meshheading:12837764-Syndrome, pubmed-meshheading:12837764-trans-Golgi Network
pubmed:year
2003
pubmed:articleTitle
Localization of mammalian NAD(P)H steroid dehydrogenase-like protein on lipid droplets.
pubmed:affiliation
Department of Molecular Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan. masato@nips.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't