The role of CHMP2B(Intron5) in autophagy and frontotemporal dementia.
The role of CHMP2B(Intron5) in autophagy and frontotemporal dementia.
复制标题
DOI：
10.1016/j.brainres.2016.02.051
复制
发表时间：
2016-10-15
期刊：
影响因子：
2.9
通讯作者：
Ahmad, S. Tariq
中科院分区：
文献类型：
--
作者：
Krasniak, Christopher S.;Ahmad, S. Tariq
荷电多泡体蛋白2B（CHMP 2B）-转运III（ESCRT-III）所需的内体复合物的组分-负责自噬和内溶酶体运输中的重要膜变形功能。CHMP 2B中的显性突变（CHMP 2BIntron 5）与遗传性额颞叶痴呆的一个子集相关-与3号染色体（FTD-3）相关的额颞叶痴呆。ESCRT-III募集Vps 4，Vps 4是一种AAA-ATP酶，在各种细胞过程中使膜活化，包括自噬和管腔内囊泡形成。CHMP 2B内含子5导致C-末端截短，去除了重要的Vps 4结合位点，并消除了CHMP 2B的正常自身抑制静息状态。CHMP 2B在大多数细胞类型中表达，但似乎对适当的神经元功能特别重要。CHMP 2BIntron 5介导的表型包括跨膜受体的错误调节、多层结构的积累、异常溶酶体形态、脑特异性微小RNA（miRNA-124）的下调、异常树突棘形态、树突分支减少和细胞死亡。目前，转基因果蝇、小鼠和人细胞系正被用于更好地了解CHMP 2BIntron 5诱导的FTD-3的不同表型和开发治疗方法。
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.
登录
查看更多内容
影响因子：
64.8
作者：
Cruts, Marc;Gijselinck, Ilse;Van Broeckhoven, Christine
通讯作者：
Van Broeckhoven, Christine
DOI：
10.1073/pnas.0903134106
发表时间：
2009-07-21
影响因子：
11.1
作者：
Ahmad, S. Tariq;Sweeney, Sean T.;Gao, Fen-Biao
通讯作者：
Gao, Fen-Biao
影响因子：
4
作者：
Belly, Agnes;Bodon, Gilles;Goldberg, Yves
通讯作者：
Goldberg, Yves
影响因子：
64.8
作者：
Baker, Matt;Mackenzie, Ian R.;Hutton, Mike
通讯作者：
Hutton, Mike
影响因子：
4.8
作者：
Benussi A;Padovani A;Borroni B
通讯作者：
Borroni B