Cargando…

Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress

During apoptosis, caspases degrade 8 out of ~30 nucleoporins to irreversibly demolish the nuclear pore complex. However, for poorly understood reasons, caspases are also activated during cell differentiation. Here, we show that sublethal activation of caspases during myogenesis results in the transi...

Descripción completa

Detalles Bibliográficos
Autores principales: Cho, Ukrae H, Hetzer, Martin W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476967/
https://www.ncbi.nlm.nih.gov/pubmed/37665327
http://dx.doi.org/10.7554/eLife.89066
_version_ 1785101046256762880
author Cho, Ukrae H
Hetzer, Martin W
author_facet Cho, Ukrae H
Hetzer, Martin W
author_sort Cho, Ukrae H
collection PubMed
description During apoptosis, caspases degrade 8 out of ~30 nucleoporins to irreversibly demolish the nuclear pore complex. However, for poorly understood reasons, caspases are also activated during cell differentiation. Here, we show that sublethal activation of caspases during myogenesis results in the transient proteolysis of four peripheral Nups and one transmembrane Nup. ‘Trimmed’ NPCs become nuclear export-defective, and we identified in an unbiased manner several classes of cytoplasmic, plasma membrane, and mitochondrial proteins that rapidly accumulate in the nucleus. NPC trimming by non-apoptotic caspases was also observed in neurogenesis and endoplasmic reticulum stress. Our results suggest that caspases can reversibly modulate nuclear transport activity, which allows them to function as agents of cell differentiation and adaptation at sublethal levels.
format Online
Article
Text
id pubmed-10476967
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-104769672023-09-05 Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress Cho, Ukrae H Hetzer, Martin W eLife Cell Biology During apoptosis, caspases degrade 8 out of ~30 nucleoporins to irreversibly demolish the nuclear pore complex. However, for poorly understood reasons, caspases are also activated during cell differentiation. Here, we show that sublethal activation of caspases during myogenesis results in the transient proteolysis of four peripheral Nups and one transmembrane Nup. ‘Trimmed’ NPCs become nuclear export-defective, and we identified in an unbiased manner several classes of cytoplasmic, plasma membrane, and mitochondrial proteins that rapidly accumulate in the nucleus. NPC trimming by non-apoptotic caspases was also observed in neurogenesis and endoplasmic reticulum stress. Our results suggest that caspases can reversibly modulate nuclear transport activity, which allows them to function as agents of cell differentiation and adaptation at sublethal levels. eLife Sciences Publications, Ltd 2023-09-04 /pmc/articles/PMC10476967/ /pubmed/37665327 http://dx.doi.org/10.7554/eLife.89066 Text en © 2023, Cho and Hetzer https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Cho, Ukrae H
Hetzer, Martin W
Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress
title Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress
title_full Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress
title_fullStr Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress
title_full_unstemmed Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress
title_short Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress
title_sort caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476967/
https://www.ncbi.nlm.nih.gov/pubmed/37665327
http://dx.doi.org/10.7554/eLife.89066
work_keys_str_mv AT choukraeh caspasemediatednuclearporecomplextrimmingincelldifferentiationandendoplasmicreticulumstress
AT hetzermartinw caspasemediatednuclearporecomplextrimmingincelldifferentiationandendoplasmicreticulumstress