Spatiotemporal Mislocalization of Nuclear Membrane-Associated Proteins in gamma-Irradiation-Induced Senescent Cells

0540504 - BFÚ 2021 RIV CH eng J - Journal Article
Svobodová Kovaříková, Alena - Bártová, Eva - Kovařík, Aleš - Lukášová, Emilie
Spatiotemporal Mislocalization of Nuclear Membrane-Associated Proteins in gamma-Irradiation-Induced Senescent Cells.
Cells. Roč. 9, č. 4 (2020), č. článku 999. E-ISSN 2073-4409
R&D Projects: GA ČR GC20-04109J
Institutional support: RVO:68081707
Keywords : lamin b receptor * dilated cardiomyopathy * cellular senescence * linc complex * nesprin-1 * heterochromatin
OECD category: Cell biology
Impact factor: 6.600, year: 2020
Method of publishing: Open access
https://www.mdpi.com/2073-4409/9/4/999

Cellular senescence, induced by genotoxic or replication stress, is accompanied by defects in nuclear morphology and nuclear membrane-heterochromatin disruption. In this work, we analyzed cytological and molecular changes in the linker of nucleoskeleton and cytoskeleton (LINC) complex proteins in senescence triggered by gamma-irradiation. We used human mammary carcinoma and osteosarcoma cell lines, both original and shRNA knockdown clones targeting lamin B receptor (LBR) and leading to LBR and lamin B (LB1) reduction. The expression status and integrity of LINC complex proteins (nesprin-1, SUN1, SUN2), lamin A/C, and emerin were analyzed by immunodetection using confocal microscopy and Western blot. The results show frequent mislocalization of these proteins from the nuclear membrane to cytoplasm and micronuclei and, in some cases, their fragmentation and amplification. The timing of these changes clearly preceded the onset of senescence. The LBR deficiency triggered neither senescence nor changes in the LINC protein distribution before irradiation. However, the cytological changes following irradiation were more pronounced in shRNA knockdown cells compared to original cell lines. We conclude that mislocalization of LINC complex proteins is a significant characteristic of cellular senescence phenotypes and may influence complex events at the nuclear membrane, including trafficking and heterochromatin attachment.
Permanent Link: http://hdl.handle.net/11104/0318126