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

Christian Schachtrup, Jae Kyu Ryu, Könül Mammadzada, Abdullah S Khan, Peter M Carlton, Alex Perez, Frank Christian, Natacha Le Moan, Eirini Vagena, Bernat Baeza-Raja, Victoria Rafalski, Justin P Chan, Roland Nitschke, Miles D Houslay, Mark H Ellisman, Tony Wyss-Coray, Jorge J Palop, Katerina Akassoglou

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

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)-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.

Original languageEnglish
Pages (from-to)1077-1080
Number of pages4
JournalNature Neuroscience
Volume18
Issue number8
Early online date29 Jun 2015
DOIs
Publication statusPublished - 1 Aug 2015

Keywords

  • regeneration
  • neuronal activity
  • nuclear pore complex

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