article published yes J. Sebastian Gomez-Cavazos author Martin W HETZER author 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed0000-0002-2111-992X 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. Rockefeller University Press2015 eng Cell Biology 0021-9525 1540-8140 2577891710.1083/jcb.201410047 2086671-681 yes J. S. Gomez-Cavazos and M. Hetzer, “The nucleoporin gp210/Nup210 controls muscle differentiation by regulating nuclear envelope/ER homeostasis,” <i>Journal of Cell Biology</i>, vol. 208, no. 6. Rockefeller University Press, pp. 671–681, 2015. Gomez-Cavazos, J. S., &#38; Hetzer, M. (2015). The nucleoporin gp210/Nup210 controls muscle differentiation by regulating nuclear envelope/ER homeostasis. <i>Journal of Cell Biology</i>. Rockefeller University Press. <a href="https://doi.org/10.1083/jcb.201410047">https://doi.org/10.1083/jcb.201410047</a> J.S. Gomez-Cavazos, M. Hetzer, Journal of Cell Biology 208 (2015) 671–681. Gomez-Cavazos, J. Sebastian, and Martin Hetzer. “The Nucleoporin Gp210/Nup210 Controls Muscle Differentiation by Regulating Nuclear Envelope/ER Homeostasis.” <i>Journal of Cell Biology</i>. Rockefeller University Press, 2015. <a href="https://doi.org/10.1083/jcb.201410047">https://doi.org/10.1083/jcb.201410047</a>. Gomez-Cavazos JS, Hetzer M. The nucleoporin gp210/Nup210 controls muscle differentiation by regulating nuclear envelope/ER homeostasis. <i>Journal of Cell Biology</i>. 2015;208(6):671-681. doi:<a href="https://doi.org/10.1083/jcb.201410047">10.1083/jcb.201410047</a> 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.” <i>Journal of Cell Biology</i>, vol. 208, no. 6, Rockefeller University Press, 2015, pp. 671–81, doi:<a href="https://doi.org/10.1083/jcb.201410047">10.1083/jcb.201410047</a>. 110752022-04-07T07:49:10Z2024-10-14T11:22:26Z