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Extracellular alpha‐synuclein induces calpain‐dependent overactivation of cyclin‐dependent kinase 5 in vitro
Author(s) -
Czapski Grzegorz A.,
Gąssowska Magdalena,
Wilkaniec Anna,
Cieślik Magdalena,
Adamczyk Agata
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.07.053
Subject(s) - cyclin dependent kinase 5 , calpain , extracellular , microbiology and biotechnology , kinase , phosphorylation , intracellular , alpha synuclein , chemistry , biology , protein kinase a , biochemistry , cyclin dependent kinase 2 , enzyme , medicine , disease , parkinson's disease
We found that exposure of PC12 cells to ASN increases Cdk5 activity via calpain‐dependent p25 formation and by enhancement of Cdk5 phosphorylation at Tyr15. Cdk5 and calpain inhibitors prevented ASN‐evoked cell death. Our findings, indicating the participation of Cdk5 in ASN toxicity, provide new insight into how extracellular ASN may trigger dopaminergic cell dysfunction in PD.