The nucleoporin gp210/Nup210 controls muscle differentiation by regulating nuclear envelope/ER homeostasis
Gomez-Cavazos JS, Hetzer M. 2015. The nucleoporin gp210/Nup210 controls muscle differentiation by regulating nuclear envelope/ER homeostasis. Journal of Cell Biology. 208(6), 671–681.
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Journal Article
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| English
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Author
Gomez-Cavazos, J. Sebastian;
Hetzer, MartinISTA
Corresponding author has ISTA affiliation
Abstract
Previously, we identified the nucleoporin gp210/Nup210 as a critical regulator of muscle and neuronal differentiation, but how this nucleoporin exerts its function and whether it modulates nuclear pore complex (NPC) activity remain unknown. Here, we show that gp210/Nup210 mediates muscle cell differentiation in vitro via its conserved N-terminal domain that extends into the perinuclear space. Removal of the C-terminal domain, which partially mislocalizes gp210/Nup210 away from NPCs, efficiently rescues the differentiation defect caused by the knockdown of endogenous gp210/Nup210. Unexpectedly, a gp210/Nup210 mutant lacking the NPC-targeting transmembrane and C-terminal domains is sufficient for C2C12 myoblast differentiation. We demonstrate that the endoplasmic reticulum (ER) stress-specific caspase cascade is exacerbated during Nup210 depletion and that blocking ER stress-mediated apoptosis rescues differentiation of Nup210-deficient cells. Our results suggest that the role of gp210/Nup210 in cell differentiation is mediated by its large luminal domain, which can act independently of NPC association and appears to play a pivotal role in the maintenance of nuclear envelope/ER homeostasis.
Keywords
Publishing Year
Date Published
2015-03-16
Journal Title
Journal of Cell Biology
Publisher
Rockefeller University Press
Volume
208
Issue
6
Page
671-681
ISSN
eISSN
IST-REx-ID
Cite this
Gomez-Cavazos JS, Hetzer M. The nucleoporin gp210/Nup210 controls muscle differentiation by regulating nuclear envelope/ER homeostasis. Journal of Cell Biology. 2015;208(6):671-681. doi:10.1083/jcb.201410047
Gomez-Cavazos, J. S., & Hetzer, M. (2015). The nucleoporin gp210/Nup210 controls muscle differentiation by regulating nuclear envelope/ER homeostasis. Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.201410047
Gomez-Cavazos, J. Sebastian, and Martin Hetzer. “The Nucleoporin Gp210/Nup210 Controls Muscle Differentiation by Regulating Nuclear Envelope/ER Homeostasis.” Journal of Cell Biology. Rockefeller University Press, 2015. https://doi.org/10.1083/jcb.201410047.
J. S. Gomez-Cavazos and M. Hetzer, “The nucleoporin gp210/Nup210 controls muscle differentiation by regulating nuclear envelope/ER homeostasis,” Journal of Cell Biology, vol. 208, no. 6. Rockefeller University Press, pp. 671–681, 2015.
Gomez-Cavazos JS, Hetzer M. 2015. The nucleoporin gp210/Nup210 controls muscle differentiation by regulating nuclear envelope/ER homeostasis. Journal of Cell Biology. 208(6), 671–681.
Gomez-Cavazos, J. Sebastian, and Martin Hetzer. “The Nucleoporin Gp210/Nup210 Controls Muscle Differentiation by Regulating Nuclear Envelope/ER Homeostasis.” Journal of Cell Biology, vol. 208, no. 6, Rockefeller University Press, 2015, pp. 671–81, doi:10.1083/jcb.201410047.
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PMID: 25778917
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