کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4323510 1292349 2016 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The role of CHMP2BIntron5 in autophagy and frontotemporal dementia
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
The role of CHMP2BIntron5 in autophagy and frontotemporal dementia
چکیده انگلیسی


• We review the structure and function of CHMP2B.
• We review the pathology caused by the CHMP2BIntron5 mutation.
• We discuss the future of current CHMP2BIntron5 model systems.

Charged multivesicular body protein 2B (CHMP2B) – a component of the endosomal complex required for transport-III (ESCRT-III) – is responsible for the vital membrane deformation functions in autophagy and endolysosomal trafficking. A dominant mutation in CHMP2B (CHMP2BIntron5) is associated with a subset of heritable frontotemporal dementia – frontotemporal dementia linked to chromosome 3 (FTD-3). ESCRT-III recruits Vps4, an AAA-ATPase that abscises the membrane during various cellular processes including autophagy and intraluminal vesicle formation. CHMP2BIntron5 results in a C-terminus truncation removing an important Vps4 binding site as well as eliminating the normal autoinhibitory resting state of CHMP2B. CHMP2B is expressed in most cell types but seems to be especially vital for proper neuronal function. CHMP2BIntron5-mediated phenotypes include misregulation of transmembrane receptors, accumulation of multilamellar structures, abnormal lysosomal morphology, down regulation of a brain-specific micro RNA (miRNA-124), abnormal dendritic spine morphology, decrease in dendritic arborization, and cell death. Currently, transgenic-fly,-mouse, and -human cell lines are being used to better understand the diverse phenotypes and develop therapeutic approaches for the CHMP2BIntron5-induced FTD-3.This article is part of a Special Issue entitled SI:Autophagy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1649, Part B, 15 October 2016, Pages 151–157
نویسندگان
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