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ESCRT-III controls nuclear envelope deformation induced by progerin
- Source :
- Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020), Scientific Reports
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group, 2020.
-
Abstract
- Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder, caused by mutation in the gene encoding lamin A/C, which produces a truncated protein called progerin. In cells from HGPS patients, progerin accumulates at the nuclear membrane (NM), where it causes NM deformations. In this study, we investigated whether progerin-induced NM deformation involved ESCRT-III, a protein complex that remodels nuclear and cytoplasmic membranes. The ESCRT-III protein CHMP4B was recruited to sites of aberrant NM proliferation in human cells ectopically expressing progerin and in patient-derived HGPS fibroblasts. Derepression of NM deformation in these cells was observed following depletion of CHMP4B or an ESCRT-III adaptor, ALIX. Treatment with rapamycin (which induce autophagic clearance of progerin and reverse progerin-induced cellular phenotypes) down-regulated progerin-induced NM deformation, whereas treatment with bafilomycin A1 (an inhibitor of autophagy and lysosome-based degradation) or CHMP4B depletion antagonized the effects of rapamycin. These results indicate that the ALIX-mediated ESCRT-III pathway plays a suppressive role in progerin-induced NM deformation and suggest that autophagy down-regulates progerin-induced NM deformation in a manner dependent on ESCRT-III machinery.
- Subjects :
- 0301 basic medicine
Premature aging
Cell biology
Aging
Molecular biology
Nuclear Envelope
lcsh:Medicine
Cell Cycle Proteins
Article
ESCRT
Cell Line
03 medical and health sciences
chemistry.chemical_compound
Progeria
0302 clinical medicine
medicine
Humans
Nuclear membrane
lcsh:Science
Cell Proliferation
Cell Nucleus
Sirolimus
Multidisciplinary
Endosomal Sorting Complexes Required for Transport
integumentary system
Calcium-Binding Proteins
Autophagy
lcsh:R
Bafilomycin
Fibroblasts
Lamin Type A
Progerin
medicine.disease
030104 developmental biology
medicine.anatomical_structure
chemistry
Mutation
lcsh:Q
Macrolides
030217 neurology & neurosurgery
Lamin
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....0187228b47ec3e00e4de2af1fc45e4c1