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

Nature neuroscience | 2015

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.

Pubmed ID: 26120963 RIS Download

Research resources used in this publication

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: 8P41GM103412-24
  • Agency: NIGMS NIH HHS, United States
    Id: P41 GM103412
  • Agency: NCRR NIH HHS, United States
    Id: 5P41RR004050-24
  • Agency: NINDS NIH HHS, United States
    Id: R21 NS082976
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI007334
  • Agency: NINDS NIH HHS, United States
    Id: R21NS082976
  • Agency: NIA NIH HHS, United States
    Id: AG047313
  • Agency: NINDS NIH HHS, United States
    Id: R01NS066361
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS066361
  • Agency: NCRR NIH HHS, United States
    Id: P41 RR004050
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS052189
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS051470
  • Agency: NIA NIH HHS, United States
    Id: R01 AG047313
  • Agency: NINDS NIH HHS, United States
    Id: R01NS052189
  • Agency: NINDS NIH HHS, United States
    Id: R01NS051470

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Jackson Laboratory (tool)

RRID:SCR_004633

An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.

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RRID:SCR_002655

Biomedical technology research center that develops computer-aided, advanced microscopy for the acquisition of structural and functional data in the dimensional range of 1 nm to 100 um, a range encompassing macromolecules, subcellular structures and cells. Novel specimen-staining methods, imaging instrumentsincluding intermediate high-voltage transmission electron microscopes (IVEMs) and high-speed, large-format laser-scanning light microscopesand computational capabilities are available for addressing mesoscale biological microscopy of proteins and macromolecular complexes in their cellular and tissue environments. These technologies are developed to bridge understanding of biological systems between the gross anatomical and molecular scales and to make these technologies broadly available to biomedical researchers. NCMIR provides expertise, infrastructure, technological development, and an environment in which new information about the 3D ultrastructure of tissues, cells, and macromolecular complexes may be accurately and easily obtained and analyzed. NCMIR fulfills its mission through technology development, collaboration, service, training, and dissemination. It aims to develop preparative methods and analytical approaches to 3D microscopy applicable to neurobiology and cell biology, incorporating equipment and implementing software that expand the analysis of 3D structure. The core research activities in the areas of specimen development, instrument development, and software infrastructures maximize the advantages of higher voltage electron microscopy and correlated light microscopies to make ambitious imaging studies across scales routine, and to facilitate the use of resources by biomedical researchers. NCMIR actively recruits outside users who will not only make use of these resources, but who also will drive technology development and receive training.

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