Changes in nuclear pore numbers control nuclear import and stress response of mouse hearts.
Lamin B2
MAP kinase
NFκB
Nup155
cardiac hypertrophy
cardiac remodeling
cardiomyocyte
nuclear pore
nuclear transport
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
24 10 2022
24 10 2022
Historique:
received:
19
10
2021
revised:
24
06
2022
accepted:
28
09
2022
entrez:
25
10
2022
pubmed:
26
10
2022
medline:
28
10
2022
Statut:
ppublish
Résumé
Nuclear pores are essential for nuclear-cytoplasmic transport. Whether and how cells change nuclear pores to alter nuclear transport and cellular function is unknown. Here, we show that rat heart muscle cells (cardiomyocytes) undergo a 63% decrease in nuclear pore numbers during maturation, and this changes their responses to extracellular signals. The maturation-associated decline in nuclear pore numbers is associated with lower nuclear import of signaling proteins such as mitogen-activated protein kinase (MAPK). Experimental reduction of nuclear pore numbers decreased nuclear import of signaling proteins, resulting in decreased expression of immediate-early genes. In a mouse model of high blood pressure, reduction of nuclear pore numbers improved adverse heart remodeling and reduced progression to lethal heart failure. The decrease in nuclear pore numbers in cardiomyocyte maturation and resulting functional changes demonstrate how terminally differentiated cells permanently alter their handling of information flux across the nuclear envelope and, with that, their behavior.
Identifiants
pubmed: 36283391
pii: S1534-5807(22)00719-5
doi: 10.1016/j.devcel.2022.09.017
pmc: PMC9614572
mid: NIHMS1841489
pii:
doi:
Substances chimiques
Nuclear Pore Complex Proteins
0
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2397-2411.e9Subventions
Organisme : NINDS NIH HHS
ID : R21 NS121706
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151386
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL155597
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL129949
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001857
Pays : United States
Organisme : NIBIB NIH HHS
ID : R21 EB023507
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151415
Pays : United States
Organisme : NIH HHS
ID : S10 OD011967
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
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