Nuclear pore complex remodeling by p75(NTR) cleavage controls TGF-beta signaling and astrocyte functions

Schachtrup Christian<sup>*</sup>; Ryu Jae Kyu; Mammadzada Koenuel; 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

doi:10.1038/nn.4054

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Nuclear pore complex remodeling by p75(NTR) cleavage controls TGF-beta signaling and astrocyte functions

作者：Schachtrup Christian^*; Ryu Jae Kyu; Mammadzada Koenuel; 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

来源：Nature Neuroscience, 2015, 18(8): 1077-+.

DOI：10.1038/nn.4054

摘要

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)-beta 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.