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

0539821 - ÚMG 2021 RIV US eng J - Článek v odborném periodiku
Takahashi, Y. - Hiratsuka, S. - Machida, N. - Takahashi, D. - Matsushita, J. - Hozák, Pavel - Misteli, T. - Miyamoto, K. - Harata, M.
Impairment of nuclear F-actin formation and its relevance to cellular phenotypes in Hutchinson-Gilford progeria syndrome.
Nucleus. Roč. 11, č. 1 (2020), s. 250-263. ISSN 1949-1034. E-ISSN 1949-1042
Grant CEP: GA ČR GA19-05608S
Institucionální podpora: RVO:68378050
Klíčová slova: Nuclear actin * lamin * nuclear organization * Hutchinson-Gilford progeria syndrome * progerin * gene expression
Obor OECD: Cell biology
Impakt faktor: 4.197, rok: 2020
Způsob publikování: Open access
https://www.tandfonline.com/doi/full/10.1080/19491034.2020.1815395

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/beta-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.
Trvalý link: http://hdl.handle.net/11104/0317521