کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7692075 | 1496263 | 2018 | 46 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Niemann-Pick C2 protein regulates sterol transport between plasma membrane and late endosomes in human fibroblasts
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کلمات کلیدی
DehydroergosterolLate endosomes/lysosomesACATMSDRESROIFRAPNPC1NPC2TGNLPDs - LPD هاsphingomyelin - اسفنگومیلینDIT - اینRecycling endosomes - بازیافت آندوسومCho - برایProbability density function - تابع چگالی احتمالChinese hamster ovarian - تخمدان هامستر چینیMean Square Displacement - جابجایی میدان متوسطKinetics - سینتیک (جنبش شناسی) Trans-Golgi network - شبکه Trans-Goljiendoplasmic reticulum - شبکه آندوپلاسمی Diffusion coefficient - ضریب انتشارPlasma membrane - غشای پلاسماphosphatidylcholine - فسفاتیدیل کولینfluorescence recovery after photobleaching - فلوئورسانس پس از فوتوبلاسیکLysosome - لیزوزومregion of interest - منطقه مورد نظرDHE - وDiffusion - واپخش یا انتشار Pdf - پی دی افcholesterol - کلسترول
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی (عمومی)
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Niemann-Pick C2 protein regulates sterol transport between plasma membrane and late endosomes in human fibroblasts Niemann-Pick C2 protein regulates sterol transport between plasma membrane and late endosomes in human fibroblasts](/preview/png/7692075.png)
چکیده انگلیسی
Niemann-Pick disease type C2 is a lipid storage disorder in which mutations in the NPC2 protein cause accumulation of lipoprotein-derived cholesterol in late endosomes and lysosomes (LE/LYSs). Whether cholesterol delivered by other means to NPC2 deficient cells also accumulates in LE/LYSs is currently unknown. We show that the close cholesterol analog dehydroergosterol (DHE), when delivered to the plasma membrane (PM) accumulates in LE/LYSs of human fibroblasts lacking functional NPC2. We measured two different time scales of sterol diffusion; while DHE rich LE/LYSs moved by slow anomalous diffusion in disease cells (Dâ¯â¼â¯4.6â10â4â¯Î¼m2/sec; αâ¼0.76), a small pool of sterol could exchange rapidly with Dâ¯â¼â¯3â¯Î¼m2/s between LE/LYSs, as shown by fluorescence recovery after photobleaching (FRAP). By quantitative lipid mass spectrometry we found that esterification of 13C-labeled cholesterol but not of DHE is reduced 10-fold in disease fibroblasts compared to control cells. Internalized NPC2 rescued the sterol storage phenotype and strongly expanded the dynamic sterol pool seen in FRAP experiments. Together, our study shows that cholesterol esterification and trafficking of sterols between the PM and LE/LYSs depends on a functional NPC2 protein. NPC2 likely acts inside LE/LYSs from where it increases non-vesicular sterol exchange with other organelles.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemistry and Physics of Lipids - Volume 213, July 2018, Pages 48-61
Journal: Chemistry and Physics of Lipids - Volume 213, July 2018, Pages 48-61
نویسندگان
Zane Berzina, Lukasz M. Solanko, Ahmed S. Mehadi, Maria Louise V. Jensen, Frederik W. Lund, Maciej Modzel, Maria Szomek, Katarzyna A. Solanko, Alice Dupont, Gitte Krogh Nielsen, Christian W. Heegaard, Christer S. Ejsing, Daniel Wüstner,