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Updated: Jun 5, 2026
06:23
Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence
Published on: January 17, 2025
Progerin-induced nuclear envelope remodeling is shaped by cell division and NUP153
Ayse Mubine Turkmen1, Jing Wang2, Adam Frost3
1Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
Journal of Cell Science
|June 4, 2026
Summary
Progerin, a mutant lamin A causing Hutchinson Gilford Progeria Syndrome (HGPS), causes distinct nuclear envelope remodeling stages. Early changes affect the inner membrane, leading to lobulated nuclei after cell division.
Area of Science:
- Cell Biology
- Aging Research
- Molecular Biology
Background:
- The nuclear envelope (NE) remodels during aging and diseases like Hutchinson Gilford Progeria Syndrome (HGPS).
- The exact mechanisms and co-factors driving NE morphological changes in HGPS are not fully understood.
- Progerin, a mutant lamin A, is a key factor in HGPS pathogenesis.
Purpose of the Study:
- To characterize the distinct stages of NE remodeling induced by progerin.
- To investigate the role of specific proteins, including NUP153, in progerin-mediated NE changes.
- To understand the cellular basis of nuclear abnormalities in aging and HGPS.
Main Methods:
- Utilized an inducible cell-based system for progerin expression.
- Employed correlative light and electron microscopy for high-resolution imaging of NE structure.
- Performed live and fixed cell imaging to track NE dynamics during the cell cycle.
- Used gene depletion (NUP153) to assess its role in NE remodeling.
Main Results:
- Progerin induces distinct NE remodeling stages: initial inner nuclear membrane (INM) alterations followed by nuclear lobulation post-division.
- Progerin accumulation sites in the INM are enriched in specific INM proteins and NUP153, excluding nuclear pore complexes.
- NUP153 depletion reduced progerin-induced INM foci, suggesting it promotes or stabilizes NE invagination.
- Cells expressing progerin exhibit pronounced nuclear lobulations characteristic of HGPS after cell division.
Conclusions:
- Progerin-induced NE remodeling occurs in a stepwise manner, with distinct interphase and post-mitotic events.
- NUP153 plays a role in stabilizing or promoting progerin-mediated INM invaginations.
- Understanding these NE remodeling stages provides insights into cellular aging and HGPS pathology.
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