Changes in nuclear pore numbers control nuclear import and stress response of mouse hearts

Lu Han, Jocelyn D. Mich-Basso, Yao Li, Niyatie Ammanamanchi, Jianquan Xu, Anita P. Bargaje, Honghai Liu, Liwen Wu, Jong Hyeon Jeong, Jonathan Franks, Donna B. Stolz, Yijen L. Wu, Dhivyaa Rajasundaram, Yang Liu, Bernhard Kühn

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2397-2411.e9
JournalDevelopmental cell
Volume57
Issue number20
DOIs
StatePublished - Oct 24 2022
Externally publishedYes

Keywords

  • cardiac hypertrophy
  • cardiac remodeling
  • cardiomyocyte
  • Lamin B2
  • MAP kinase
  • NFκB
  • nuclear pore
  • nuclear transport
  • Nup155

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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