Nuclear pore complex remodeling by p75NTR cleavage controls TGF-[beta] signaling and astrocyte functions

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 sign...

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Published inNature neuroscience Vol. 18; no. 8; p. 1077
Main Authors 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
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group 01.08.2015
Subjects
Growth factors
Kinases
Localization
La Jolla California
San Francisco California
United Kingdom > UK
United States > US
California
Germany
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Summary: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.
ISSN:1097-6256
1546-1726
DOI:10.1038/nn.4054