Tissue transglutaminase is not involved in the aggregate formation of stably expressed alpha-synuclein in SH-SY5Y human neuroblastoma cells.
Intraneuronal deposition containing alpha-synuclein is implicated in the pathogenesis of synuclein-opathies including Parkinsons disease (PD). Although it has been demonstrated that cytoplasmic inclusions of wild type alpha-synuclein are observed in the brain of PD patients and that alpha-synuclein mutations such as A30P and A53T accelerate aggregate formation, the exact mechanism by which alpha-synuclein forms insoluble aggregates is still controversial. In the present study, to understand the possible involvement of tissue transglutaminase (tTG) in aggregate formation of alpha-synuclein, SH-SY5Y cell lines stably expressing wild type or mutant (A30P or A53T) alpha-synuclein were created and aggregate formation of alpha-synuclein was observed upon activation of tTG. The data demonstrated that alpha-synuclein negligibly interacted with tTG and that activation of tTG did not result in the aggregate formation of alpha-synuclein in SH-SY5Y cells overexpressing either wild type or mutant alpha-synuclein. In addition, alpha-synuclein was not modified by activated tTG in situ. These data suggest that tTG is unlikely to be a contributing factor to the formation of aggregates of alpha-synuclein in a stable cell model.
Suh
Myung-Duk
MD
Department of Pharmacology, College of Medicine, Kangwon National University, Chunchon 200-701, Korea.
Park
Chang-Ha
CH
Kim
Sung-Soo
SS
Kil
Myeng-Og
MO
Lee
Geon-Hee
GH
Johnson
Gail V W
GV
Chun
Wanjoo
W
D045744:Cell Line, Tumor; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051843:Synucleins; D011503:Transglutaminases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins