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Neurobiology
2015
Nature neuroscience
Nuclear pore complex remodeling by p75NTR cleavage controls TGF-β signaling and astrocyte functions
Authors:
Schachtrup, C., Ryu, J. K., Mammadzada, K., Khan, A. S., Carlton, P. M., Perez, A., ... & Akassoglou, K.
Abstract:
Astrocytes modulate neuronal activity and inhibit regeneration. We show that cleaved p75 neurotrophin receptor (p75NTR) 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 p75NTR interacts with nucleoporins to promote Smad2 nucleocytoplasmic shuttling. Thus, NPC remodeling by regulated intramembrane cleavage of p75NTR controls astrocyte–neuronal communication in response to profibrotic factors.