title: Nuclear pore complex remodeling by p75(NTR) cleavage controls TGF-β 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)-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.
authors.affiliation: 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Schachtrup
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, California, USA.
authors.forename: Jae Kyu
authors.initials: JK
authors.lastname: Ryu
authors.affiliation: 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.
authors.forename: Könül
authors.initials: K
authors.lastname: Mammadzada
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, California, USA.
authors.forename: Abdullah S
authors.initials: AS
authors.lastname: Khan
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Peter M
authors.identifier: 0000000253206024
authors.initials: PM
authors.lastname: Carlton
authors.affiliation: 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.
authors.forename: Alex
authors.initials: A
authors.lastname: Perez
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Christian
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, California, USA.
authors.forename: Natacha
authors.initials: N
authors.lastname: Le Moan
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, California, USA.
authors.forename: Eirini
authors.initials: E
authors.lastname: Vagena
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, California, USA.
authors.forename: Bernat
authors.initials: B
authors.lastname: Baeza-Raja
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, California, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Rafalski
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, California, USA.
authors.forename: Justin P
authors.initials: JP
authors.lastname: Chan
authors.affiliation: 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.
authors.forename: Roland
authors.initials: R
authors.lastname: Nitschke
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, UK.
authors.forename: Miles D
authors.initials: MD
authors.lastname: Houslay
authors.affiliation: 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.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ellisman
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Wyss-Coray
authors.affiliation: 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.
authors.forename: Jorge J
authors.initials: JJ
authors.lastname: Palop
authors.affiliation: 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.
authors.forename: Katerina
authors.identifier: 0000000226321465
authors.initials: K
authors.lastname: Akassoglou
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology; D004569:Electroencephalography; D065818:Gamma Rhythm / Q000502:physiology*; D005911:Gliosis / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006849:Hydrocephalus / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology*; D041681:NIH 3T3 Cells; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D028861:Nuclear Pore Complex Proteins; D020800:Receptor, Nerve Growth Factor; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D016212:Transforming Growth Factor beta