Nuclear Pore Complexes Cluster in Dysmorphic Nuclei of Normal and Progeria Cells during Replicative Senescence
Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disease caused by a mutation in <i>LMNA</i>. A G608G mutation in exon 11 of <i>LMNA</i> is responsible for most HGPS cases, generating a truncated protein called “progerin”. Progerin is permanently farnesyl...
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doaj-04d80d1dd08048d2a4c9ec61210675e02021-01-15T00:01:27ZengMDPI AGCells2073-44092021-01-011015315310.3390/cells10010153Nuclear Pore Complexes Cluster in Dysmorphic Nuclei of Normal and Progeria Cells during Replicative SenescenceJennifer M. Röhrl0Rouven Arnold1Karima Djabali2Epigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine, Technical University of Munich (TUM), 85748 Garching, GermanyEpigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine, Technical University of Munich (TUM), 85748 Garching, GermanyEpigenetics of Aging, Department of Dermatology and Allergy, TUM School of Medicine, Technical University of Munich (TUM), 85748 Garching, GermanyHutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disease caused by a mutation in <i>LMNA</i>. A G608G mutation in exon 11 of <i>LMNA</i> is responsible for most HGPS cases, generating a truncated protein called “progerin”. Progerin is permanently farnesylated and accumulates in HGPS cells, causing multiple cellular defects such as nuclear dysmorphism, a thickened lamina, loss of heterochromatin, premature senescence, and clustering of Nuclear Pore Complexes (NPC). To identify the mechanism of NPC clustering in HGPS cells, we evaluated post-mitotic NPC assembly in control and HGPS cells and found no defects. Next, we examined the occurrence of NPC clustering in control and HGPS cells during replicative senescence. We reported that NPC clustering occurs solely in the dysmorphic nuclei of control and HGPS cells. Hence, NPC clustering occurred at a higher frequency in HGPS cells compared to control cells at early passages; however, in late cultures with similar senescence index, NPCs clustering occurred at a similar rate in both control and HGPS. Our results show that progerin does not disrupt post-mitotic reassembly of NPCs. However, NPCs frequently cluster in dysmorphic nuclei with a high progerin content. Additionally, nuclear envelope defects that arise during replicative senescence cause NPC clustering in senescent cells with dysmorphic nuclei.https://www.mdpi.com/2073-4409/10/1/153progerinnuclear poremitosisreplicative senescenceprogerianuclear envelope |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jennifer M. Röhrl Rouven Arnold Karima Djabali |
spellingShingle |
Jennifer M. Röhrl Rouven Arnold Karima Djabali Nuclear Pore Complexes Cluster in Dysmorphic Nuclei of Normal and Progeria Cells during Replicative Senescence Cells progerin nuclear pore mitosis replicative senescence progeria nuclear envelope |
author_facet |
Jennifer M. Röhrl Rouven Arnold Karima Djabali |
author_sort |
Jennifer M. Röhrl |
title |
Nuclear Pore Complexes Cluster in Dysmorphic Nuclei of Normal and Progeria Cells during Replicative Senescence |
title_short |
Nuclear Pore Complexes Cluster in Dysmorphic Nuclei of Normal and Progeria Cells during Replicative Senescence |
title_full |
Nuclear Pore Complexes Cluster in Dysmorphic Nuclei of Normal and Progeria Cells during Replicative Senescence |
title_fullStr |
Nuclear Pore Complexes Cluster in Dysmorphic Nuclei of Normal and Progeria Cells during Replicative Senescence |
title_full_unstemmed |
Nuclear Pore Complexes Cluster in Dysmorphic Nuclei of Normal and Progeria Cells during Replicative Senescence |
title_sort |
nuclear pore complexes cluster in dysmorphic nuclei of normal and progeria cells during replicative senescence |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2021-01-01 |
description |
Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disease caused by a mutation in <i>LMNA</i>. A G608G mutation in exon 11 of <i>LMNA</i> is responsible for most HGPS cases, generating a truncated protein called “progerin”. Progerin is permanently farnesylated and accumulates in HGPS cells, causing multiple cellular defects such as nuclear dysmorphism, a thickened lamina, loss of heterochromatin, premature senescence, and clustering of Nuclear Pore Complexes (NPC). To identify the mechanism of NPC clustering in HGPS cells, we evaluated post-mitotic NPC assembly in control and HGPS cells and found no defects. Next, we examined the occurrence of NPC clustering in control and HGPS cells during replicative senescence. We reported that NPC clustering occurs solely in the dysmorphic nuclei of control and HGPS cells. Hence, NPC clustering occurred at a higher frequency in HGPS cells compared to control cells at early passages; however, in late cultures with similar senescence index, NPCs clustering occurred at a similar rate in both control and HGPS. Our results show that progerin does not disrupt post-mitotic reassembly of NPCs. However, NPCs frequently cluster in dysmorphic nuclei with a high progerin content. Additionally, nuclear envelope defects that arise during replicative senescence cause NPC clustering in senescent cells with dysmorphic nuclei. |
topic |
progerin nuclear pore mitosis replicative senescence progeria nuclear envelope |
url |
https://www.mdpi.com/2073-4409/10/1/153 |
work_keys_str_mv |
AT jennifermrohrl nuclearporecomplexesclusterindysmorphicnucleiofnormalandprogeriacellsduringreplicativesenescence AT rouvenarnold nuclearporecomplexesclusterindysmorphicnucleiofnormalandprogeriacellsduringreplicativesenescence AT karimadjabali nuclearporecomplexesclusterindysmorphicnucleiofnormalandprogeriacellsduringreplicativesenescence |
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