@article{ed570604cae24c3daab71ac5c390b981,
title = "Changes in nuclear pore numbers control nuclear import and stress response of mouse hearts",
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.",
keywords = "cardiac hypertrophy, cardiac remodeling, cardiomyocyte, Lamin B2, MAP kinase, NFκB, nuclear pore, nuclear transport, Nup155",
author = "Lu Han and Mich-Basso, \{Jocelyn D.\} and Yao Li and Niyatie Ammanamanchi and Jianquan Xu and Bargaje, \{Anita P.\} and Honghai Liu and Liwen Wu and Jeong, \{Jong Hyeon\} and Jonathan Franks and Stolz, \{Donna B.\} and Wu, \{Yijen L.\} and Dhivyaa Rajasundaram and Yang Liu and Bernhard K{\"u}hn",
note = "We thank Stephen Young (University of California, Los Angeles) for providing Lmnb2 flox mice. We are grateful for technical advice from Simon Watkins (Center for Biological Imaging, University of Pittsburgh) and technical support from Samuel K. Wyman of the Animal Imaging Core at Rangos Research Center (University of Pittsburgh). We thank Kyla Holbrook and Katelyn Parsons for technical assistance (Children{\textquoteright}s Hospital of Pittsburgh). We thank members of the Kuhn laboratory and Michael Tsang (University of Pittsburgh) for support, helpful discussions, and critical reading of the manuscript. This research was supported by the Richard King Mellon Foundation Institute for Pediatric Research (UPMC Children{\textquoteright}s Hospital of Pittsburgh), HeartFest , a Transatlantic Network of Excellence grant by the Leducq Foundation ( 15CVD03 ), NIH grants R01HL151415 , R01 HL151386 , and R01HL155597 , and a grant from the UPMC Aging Institute (to B.K.). This project was supported by AHA Career Development Awards (to L.H. and Y.L.W.) and by an NIH -Training Grant (to Y.L., T32HL129949 ). Y.L.W. received support from the NIH ( EB023507 , NS121706-01 ), the AHA ( 18CDA34140024 ), and the DOD ( W81XWH1810070 , W81XWH-22-1-0221 ). This research was supported through S10OD011967 (to D.B.S.). J.-H. J., and B.K. received support from the Clinical and Translational Science Institute at the University of Pittsburgh , which is supported by Clinical and Translational Science Award (CTSA) grant UL1 TR001857 . We thank Stephen Young (University of California, Los Angeles) for providing Lmnb2flox mice. We are grateful for technical advice from Simon Watkins (Center for Biological Imaging, University of Pittsburgh) and technical support from Samuel K. Wyman of the Animal Imaging Core at Rangos Research Center (University of Pittsburgh). We thank Kyla Holbrook and Katelyn Parsons for technical assistance (Children's Hospital of Pittsburgh). We thank members of the Kuhn laboratory and Michael Tsang (University of Pittsburgh) for support, helpful discussions, and critical reading of the manuscript. This research was supported by the Richard King Mellon Foundation Institute for Pediatric Research (UPMC Children's Hospital of Pittsburgh), HeartFest, a Transatlantic Network of Excellence grant by the Leducq Foundation (15CVD03), NIH grants R01HL151415, R01 HL151386, and R01HL155597, and a grant from the UPMC Aging Institute (to B.K.). This project was supported by AHA Career DevelopmentAwards (to L.H. and Y.L.W.) and by an NIH-Training Grant (to Y.L. T32HL129949). Y.L.W. received support from the NIH (EB023507, NS121706-01), the AHA (18CDA34140024), and the DOD (W81XWH1810070, W81XWH-22-1-0221). This research was supported through S10OD011967 (to D.B.S.). J.-H. J. and B.K. received support from the Clinical and Translational Science Institute at the University of Pittsburgh, which is supported by Clinical and Translational Science Award (CTSA) grant UL1 TR001857. L.H. J.M.-B. Y. Li, N.A. H.L. A.P.B. J.X. Y.Liu, Y.L.W. and J.F. designed and performed experiments, analyzed data, and prepared figure panels and manuscript parts. L.W. and D.R. analyzed data and prepared figure panels. L.H. Y.Li. Y. Liu, Y.L.W. J.-H. J. D.B.S. and B.K. directed research. All authors reviewed and edited the manuscript.",
year = "2022",
month = oct,
day = "24",
doi = "10.1016/j.devcel.2022.09.017",
language = "English (US)",
volume = "57",
pages = "2397--2411.e9",
journal = "Developmental cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "20",
}