FasL, Fas, and death-inducing signaling complex (DISC) proteins are recruited to membrane rafts after spinal cord injury.
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 cFLIP(L) . Thus, FasL/Fas-mediated signaling after SCI is similar to Fas expressing Type I cell apoptosis.
Davis
Angela R
AR
Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Lotocki
George
G
Marcillo
Alex E
AE
Dietrich
W Dalton
WD
Keane
Robert W
RW
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D021962:Membrane Microdomains / Q000378:metabolism*; D018613:Microscopy, Confocal; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology; D019014:fas Receptor / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; D053222:Fas Ligand Protein; C491898:Fas protein, rat; C505662:Faslg protein, rat; D019014:fas Receptor