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Nuclear pore complex remodeling by p75NTR cleavage controls TGF-β signaling and astrocyte functions
- Schachtrup, Christian;
- Ryu, Jae Kyu;
- Mammadzada, Könül;
- Khan, Abdullah S;
- Carlton, Peter M;
- Perez, Alex;
- Christian, Frank;
- Le Moan, Natacha;
- Vagena, Eirini;
- Baeza-Raja, Bernat;
- Rafalski, Victoria;
- Chan, Justin P;
- Nitschke, Roland;
- Houslay, Miles D;
- Ellisman, Mark H;
- Wyss-Coray, Tony;
- Palop, Jorge J;
- Akassoglou, Katerina
- et al.
Published Web Location
https://doi.org/10.1038/nn.4054Abstract
Astrocytes modulate neuronal activity and inhibit regeneration. We show that cleaved p75 neurotrophin receptor (p75(NTR)) is a component of the nuclear pore complex (NPC) required for glial scar formation and reduced gamma oscillations in mice via regulation of transforming growth factor (TGF)-β signaling. Cleaved p75(NTR) interacts with nucleoporins to promote Smad2 nucleocytoplasmic shuttling. Thus, NPC remodeling by regulated intramembrane cleavage of p75(NTR) controls astrocyte-neuronal communication in response to profibrotic factors.
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