Impairment of nuclear F-actin formation and its relevance to cellular phenotypes in Hutchinson-Gilford progeria syndrome

Autor: Yuto Takahashi, Shogo Hiratsuka, Nanako Machida, Daisuke Takahashi, Junpei Matsushita, Pavel Hozak, Tom Misteli, Kei Miyamoto, Masahiko Harata
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Nucleus, Vol 11, Iss 1, Pp 250-263 (2020)
Druh dokumentu: article
ISSN: 1949-1034
1949-1042
19491034
DOI: 10.1080/19491034.2020.1815395
Popis: 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.
Databáze: Directory of Open Access Journals
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