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.


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*


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