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

ABSTRACT: 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)-? 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.

SUBMITTER: Schachtrup C

PROVIDER: S-EPMC4878404 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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

Schachtrup Christian C Ryu Jae Kyu JK Mammadzada Könül K Khan Abdullah S AS Carlton Peter M PM Perez Alex A Christian Frank F Le Moan Natacha N Vagena Eirini E Baeza-Raja Bernat B Rafalski Victoria V Chan Justin P JP Nitschke Roland R Houslay Miles D MD Ellisman Mark H MH Wyss-Coray Tony T Palop Jorge J JJ Akassoglou Katerina K

Nature neuroscience 20150629 8

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 comm ...[more]

PMID: 26120963

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