Journal ArticleDOI
Identification of HE1 as the Second Gene of Niemann-Pick C Disease
Saule Naureckiene,David E. Sleat,David E. Sleat,Henry Lackland,Anthony H. Fensom,Marie T. Vanier,Robert Wattiaux,Michel Jadot,Peter Lobel,Peter Lobel +9 more
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TLDR
Treatment of NP-C2 fibroblasts with exogenous recombinant HE1 protein ameliorated lysosomal accumulation of low density lipoprotein-derived cholesterol.Abstract:
Niemann-Pick type C2 disease (NP-C2) is a fatal hereditary disorder of unknown etiology characterized by defective egress of cholesterol from lysosomes. Here we show that the disease is caused by a deficiency in HE1, a ubiquitously expressed lysosomal protein identified previously as a cholesterol-binding protein. HE1 was undetectable in fibroblasts from NP-C2 patients but present in fibroblasts from unaffected controls and NP-C1 patients. Mutations in the HE1 gene, which maps to chromosome 14q24.3, were found in NP-C2 patients but not in controls. Treatment of NP-C2 fibroblasts with exogenous recombinant HE1 protein ameliorated lysosomal accumulation of low density lipoprotein-derived cholesterol.read more
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The crystal structure of a major dust mite allergen Der p 2, and its biological implications.
Urszula Derewenda,J. Li,Zygmunt S. Derewenda,Zbigniew Dauter,Geoffrey A. Mueller,Geoffrey A. Mueller,Gordon S. Rule,David C. Benjamin,David C. Benjamin +8 more
TL;DR: The crystal structure of the common house mite (Dermatophagoides sp.) Der p 2 allergen was solved at 2.15 A resolution using the MAD phasing technique, and reveals an immunoglobulin-like tertiary fold.
Journal ArticleDOI
Niemann-Pick C Variant Detection by Altered Sphingolipid Trafficking and Correlation with Mutations within a Specific Domain of NPC1
Xiaofeng Sun,David L. Marks,Walter D. Park,Christine L. Wheatley,Vishwajeet Puri,John F. O'Brien,Daniel L. Kraft,Patrick A. Lundquist,Marc C. Patterson,Richard E. Pagano,Karen Snow +10 more
TL;DR: It is demonstrated that NPC-variant fibroblast samples can be detected as sphingolipid storage disease cells, using a fluorescent sphingoipid analog, BODIPY-lactosylceramide, and found that 5 of the 12 variant cell samples had no apparent defect in NPC1 but were otherwise indistinguishable from other variant cells.
Journal ArticleDOI
START domain proteins and the intracellular trafficking of cholesterol in steroidogenic cells.
TL;DR: The intracellular trafficking of cholesterol in steroidogenic cells plays an important role in the regulation of hormone synthesis and recently evidence indicates that a family of proteins related to the steroidogenic acute regulatory protein (StAR) perform critical functions in moving the sterol substrate to the mitochondrial inner membrane.
Journal ArticleDOI
Niemann-Pick C Disease and Mobilization of Lysosomal Cholesterol by Cyclodextrin
Jean E. Vance,Barbara Karten +1 more
TL;DR: The molecular mechanisms leading to Niemann-Pick type C disease, particularly in the CNS, are summarized and recent exciting data on the mechanism by which the cholesterol-sequestering agent cyclodextrin can bypass the functions of NPC1 and NPC2 in the LEs/Ls, and mobilize cholesterol from LEs/, will be highlighted.
Journal ArticleDOI
O-Fucosylation of Notch Occurs in the Endoplasmic Reticulum
Yi Luo,Robert S. Haltiwanger +1 more
TL;DR: Analysis of the subcellular localization of protein O-FucT-1, which is responsible for adding O-fucose to epidermal growth factor-like repeats, reveals that it is a soluble protein that localizes to the endoplasmic reticulum (ER) and suggests that it may play a role in quality control.
References
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Book
The Metabolic and Molecular Bases of Inherited Disease
TL;DR: In this paper, the authors present a list of disorders of MITOCHONDRIAL FUNCTION, including the following: DISORDERS OF MIOCHONDRIC FERTILITY XIX, XVI, XIX.
Journal ArticleDOI
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Journal ArticleDOI
Association of Mutations in a Lysosomal Protein with Classical Late-Infantile Neuronal Ceroid Lipofuscinosis
David E. Sleat,Robert J. Donnelly,Henry Lackland,Henry Lackland,Chang Gong Liu,Istvan Sohar,Istvan Sohar,Raju K. Pullarkat,Peter Lobel,Peter Lobel +9 more
TL;DR: In this paper, the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an affinity marker, and a single protein was identified that is absent in LINCL.
Journal ArticleDOI
Niemann–Pick C1 Is a Late Endosome-Resident Protein That Transiently Associates with Lysosomes and the Trans-Golgi Network
TL;DR: Characterizing the subcellular location of the NPC1 protein suggests that U18666A may inhibit the retrograde transport of NPC1 from lysosomes to late endosomes for subsequent transfer to the trans-Golgi network.
Journal Article
Genetic heterogeneity in Niemann-Pick C disease: a study using somatic cell hybridization and linkage analysis.
TL;DR: In this article, the authors conducted a study on skin fibroblast cultures from 32 unrelated Niemann-Pick C patients covering the range of known clinical and biochemical phenotypes.
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