Changes in nuclear pore numbers control nuclear import and stress response of mouse hearts. Academic Article uri icon

Overview

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.

publication date

  • October 24, 2022

Research

keywords

  • Nuclear Envelope
  • Nuclear Pore

Identity

PubMed Central ID

  • PMC9614572

Scopus Document Identifier

  • 85140675071

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2022.09.017

PubMed ID

  • 36283391

Additional Document Info

volume

  • 57

issue

  • 20