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

doi:10.1038/nn.4054

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

Nat Neurosci. 2015 Aug;18(8):1077-80. doi: 10.1038/nn.4054. Epub 2015 Jun 29.

Authors

Christian Schachtrup¹, Jae Kyu Ryu², Könül Mammadzada³, Abdullah S Khan², Peter M Carlton⁴, Alex Perez⁵, Frank Christian⁶, Natacha Le Moan², Eirini Vagena², Bernat Baeza-Raja², Victoria Rafalski², Justin P Chan², Roland Nitschke⁷, Miles D Houslay⁸, Mark H Ellisman⁵, Tony Wyss-Coray⁹, Jorge J Palop¹⁰, Katerina Akassoglou¹⁰

Affiliations

¹ 1] Gladstone Institute of Neurological Disease, University of California, San Francisco, California, USA. [2] Institute of Anatomy and Cell Biology, Department of Molecular Embryology, University of Freiburg, Freiburg, Germany.
² Gladstone Institute of Neurological Disease, University of California, San Francisco, California, USA.
³ 1] Institute of Anatomy and Cell Biology, Department of Molecular Embryology, University of Freiburg, Freiburg, Germany. [2] Faculty of Biology, University of Freiburg, Freiburg, Germany.
⁴ Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA.
⁵ 1] Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. [2] National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, California, USA.
⁶ Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
⁷ 1] Life Imaging Center, Center for Biological Systems Analysis, University of Freiburg, Freiburg, Germany. [2] BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany.
⁸ Institute of Pharmaceutical Science, King's College London, London, UK.
⁹ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
¹⁰ 1] Gladstone Institute of Neurological Disease, University of California, San Francisco, California, USA. [2] Department of Neurology, University of California, San Francisco, San Francisco, California, USA.

PMID: 26120963
PMCID: PMC4878404
DOI: 10.1038/nn.4054

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Astrocytes / metabolism*
Behavior, Animal / physiology
Electroencephalography
Gamma Rhythm / physiology*
Gliosis / metabolism
HEK293 Cells
Humans
Hydrocephalus / metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Motor Activity / physiology*
NIH 3T3 Cells
Nuclear Pore / metabolism*
Nuclear Pore Complex Proteins / metabolism
Receptor, Nerve Growth Factor / deficiency
Receptor, Nerve Growth Factor / metabolism*
Signal Transduction*
Smad2 Protein / metabolism
Transforming Growth Factor beta / metabolism*

Substances

Nuclear Pore Complex Proteins
Receptor, Nerve Growth Factor
Smad2 Protein
Smad2 protein, mouse
Transforming Growth Factor beta

Abstract

Publication types

MeSH terms

Substances

Grants and funding