Impairment of nuclear F-actin formation and its relevance to cellular phenotypes in Hutchinson-Gilford progeria syndrome.
Impairment of nuclear F-actin formation and its relevance to cellular phenotypes in Hutchinson-Gilford progeria syndrome.
复制标题
DOI：
10.1080/19491034.2020.1815395
复制
发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Harata M
中科院分区：
文献类型：
--
作者：
Takahashi Y;Hiratsuka S;Machida N;Takahashi D;Matsushita J;Hozak P;Misteli T;Miyamoto K;Harata M
Hutchinson-Gilford早衰综合征（HGPS）是由核纤层蛋白A突变引起的一种过早衰老疾病，核纤层蛋白A有助于核结构和核中染色质的空间组织。核纤层蛋白A突变体（称为早老蛋白）的表达导致核组织的功能和结构破坏。由于早老蛋白缺乏核纤层蛋白A的肌动蛋白结合位点的一部分，我们假设核肌动蛋白的动力学和功能在HGPS细胞中改变。核F-肌动蛋白是核形状组织、转录调控、DNA损伤修复和Wnt/β-catenin信号传导激活所必需的。在这里，我们表明，早老蛋白的表达减少核F-肌动蛋白和F-肌动蛋白调节的转录受损。当核F-肌动蛋白水平通过核靶向肌动蛋白的过度表达或通过使用jasplakinelatin（一种稳定F-肌动蛋白的化合物）增加时，核形状的不规则性和基因表达的缺陷可以逆转。这些观察结果为核肌动蛋白与HGPS病因学之间的新关系提供了证据。
Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a mutation of lamin A, which contributes to nuclear architecture and the spatial organization of chromatin in the nucleus. The expression of a lamin A mutant, named progerin, leads to functional and structural disruption of nuclear organization. Since progerin lacks a part of the actin-binding site of lamin A, we hypothesized that nuclear actin dynamics and function are altered in HGPS cells. Nuclear F-actin is required for the organization of nuclear shape, transcriptional regulation, DNA damage repair, and activation of Wnt/β-catenin signaling. Here we show that the expression of progerin decreases nuclear F-actin and impairs F-actin-regulated transcription. When nuclear F-actin levels are increased by overexpression of nuclear-targeted actin or by using jasplakinolide, a compound that stabilizes F-actin, the irregularity of nuclear shape and defects in gene expression can be reversed. These observations provide evidence for a novel relationship between nuclear actin and the etiology of HGPS.
登录
查看更多内容
影响因子：
7.5
作者：
Gonzalo S;Kreienkamp R
通讯作者：
Kreienkamp R
影响因子：
56.9
作者：
Baarlink, Christian;Wang, Haicui;Grosse, Robert
通讯作者：
Grosse, Robert
影响因子：
11.8
作者：
Hernandez, Lidia;Roux, Kyle J.;Stewart, Colin L.
通讯作者：
Stewart, Colin L.
影响因子：
--
作者：
Izdebska M;Zielińska W;Grzanka D;Gagat M
通讯作者：
Gagat M
影响因子：
11.4
作者：
Chatzifrangkeskou, Maria;Pefani, Dafni-Eleftheria;O'Neill, Eric
通讯作者：
O'Neill, Eric