Fragmentation of Golgi complex and Golgi autoantigens during apoptosis and necrosis.
Anti-Golgi complex autoantibodies are found primarily in patients with Sjögren's syndrome and systemic lupus erythematosus, although they are not restricted to these diseases. Several Golgi autoantigens have been identified that represent a small family of proteins. Common features of all Golgi autoantigens appear to be their distinct structural organization of multiple alpha-helical coiled-coil rods in the central domains flanked by non-coiled-coil N-termini and C-termini, and their localization to the cytoplasmic face of Golgi cisternae. Many autoantigens in systemic autoimmune diseases have distinct cleavage products in apoptosis or necrosis and this has raised the possibility that cell death may play a role in the generation of potentially immunostimulatory forms of autoantigens. In the present study, we examined changes in the Golgi complex and associated autoantigens during apoptosis and necrosis. Immunofluorescence analysis showed that the Golgi complex was altered and developed distinctive characteristics during apoptosis and necrosis. In addition, immunoblotting analysis showed the generation of antigenic fragments of each Golgi autoantigen, suggesting that they may play a role in sustaining autoantibody production. Further studies are needed to determine whether the differences observed in the Golgi complex during apoptosis or necrosis may account for the production of anti-Golgi complex autoantibodies.
Nozawa
Kazuhisa
K
Department of Molecular and Experimental Medicine, WM Keck Autoimmune Disease Center, The Scripps Research Institute, La Jolla, California 92037, USA.
Casiano
Carlos A
CA
Hamel
John C
JC
Molinaro
Christine
C
Fritzler
Marvin J
MJ
Chan
Edward K L
EK
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology* / Q000648:ultrastructure*; D015551:Autoimmunity / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D019084:Fluorescent Antibody Technique, Indirect; D006056:Golgi Apparatus / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure*; D022781:Hepatocytes; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D008565:Membrane Proteins; D009336:Necrosis; D019311:Staurosporine / Q000633:toxicity
D001324:Autoantigens; D008565:Membrane Proteins; C404952:golgin-67; D019311:Staurosporine