P45 forms a complex with FADD and promotes neuronal cell survival following spinal cord injury

PLoS One. 2013 Jul 23;8(7):e69286. doi: 10.1371/journal.pone.0069286. Print 2013.

Abstract

Fas-associated death domain (DD) adaptor (FADD), a member of the DD superfamily, contains both a DD and a death effector domain (DED) that are important in mediating FAS ligand-induced apoptotic signaling. P45 is a unique member of the DD superfamily in that it has a domain with sequence and structural characteristics of both DD and DED. We show that p45 forms a complex with FADD and diminishes Fas-FADD mediated death signaling. The DED of FADD is required for the complex formation with p45. Following spinal cord injury, transgenic mice over-expressing p45 exhibit increased neuronal survival, decreased retraction of corticospinal tract fibers and improved functional recovery. Understanding p45-mediated cellular and molecular mechanisms may provide insights into facilitating nerve regeneration in humans.

Publication types

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

MeSH terms

  • Animals
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Cell Death
  • Cell Survival
  • Enzyme Activation
  • Fas Ligand Protein / metabolism
  • Fas-Associated Death Domain Protein / chemistry
  • Fas-Associated Death Domain Protein / metabolism*
  • Female
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Neurons / metabolism*
  • Neurons / pathology*
  • Protein Structure, Tertiary
  • Receptors, Death Domain / metabolism*
  • Signal Transduction
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology*
  • Thy-1 Antigens / metabolism

Substances

  • Fadd protein, mouse
  • Fas Ligand Protein
  • Fas-Associated Death Domain Protein
  • Membrane Glycoproteins
  • Nradd protein, mouse
  • Receptors, Death Domain
  • Thy-1 Antigens
  • Caspase 3
  • Caspase 8