FasL, Fas, and death-inducing signaling complex (DISC) proteins are recruited to membrane rafts after spinal cord injury

Angela R. Davis, George Lotocki, Alexander Marcillo, W. Dalton Dietrich, Robert Keane

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The Fas/CD95 receptor-ligand system plays an essential role in apoptosis that contributes to secondary damage after spinal cord injury (SCI), but the mechanism regulating the efficiency of FasL/Fas signaling in the central nervous system (CNS) is unknown. Here, FasL/Fas signaling complexes in membrane rafts were investigated in the spinal cord of adult female Fischer rats subjected to moderate cervical SCI and sham operation controls. In sham-operated animals, a portion of FasL, but not Fas was present in membrane rafts. SCI resulted in FasL and Fas translocation into membrane raft microdomains where Fas associates with the adaptor proteins Fas-associated death domain (FADD), caspase-8, cellular FLIP long form (cFLIPL), and caspase-3, forming a death-inducing signaling complex (DISC). Moreover, SCI induced expression of Fas in clusters around the nucleus in both neurons and astrocytes. The formation of the DISC signaling platform leads to rapid activation of initiator caspase-8 and effector caspase-3, and the modification of signaling intermediates such as FADD and cFLIPL. Thus, FasL/Fas-mediated signaling after SCI is similar to Fas expressing Type I cell apoptosis.

Original languageEnglish
Pages (from-to)823-834
Number of pages12
JournalJournal of Neurotrauma
Volume24
Issue number5
DOIs
StatePublished - May 1 2007

Fingerprint

Death Domain Receptor Signaling Adaptor Proteins
Spinal Cord Injuries
CASP8 and FADD-Like Apoptosis Regulating Protein
Membranes
Caspase 8
Caspase 3
Fas-Associated Death Domain Protein
Initiator Caspases
Effector Caspases
Apoptosis
Membrane Microdomains
CD95 Antigens
Fas Ligand Protein
Inbred F344 Rats
Astrocytes
Spinal Cord
Central Nervous System
Neurons

Keywords

  • Apoptosis
  • Fas
  • Fasl
  • Intracellular signaling
  • Membrane rafts
  • Spinal cord injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

FasL, Fas, and death-inducing signaling complex (DISC) proteins are recruited to membrane rafts after spinal cord injury. / Davis, Angela R.; Lotocki, George; Marcillo, Alexander; Dalton Dietrich, W.; Keane, Robert.

In: Journal of Neurotrauma, Vol. 24, No. 5, 01.05.2007, p. 823-834.

Research output: Contribution to journalArticle

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