Constitutive Phosphorylation of the Parkinson's Disease Associated α-Synuclein *

摘要: Abstract α-Synuclein has been implicated in the pathogenesis of Parkinson's disease, since rare autosomal dominant mutations are associated with early onset disease and α-synuclein was found to be a major constituent Lewy bodies. We have analyzed expression transfected cell lines. In pulse-chase experiments appeared stable over long periods (t 54 h) no endoproteolytic processing observed. constitutively phosphorylated human kidney 293 cells as well rat pheochromocytoma PC12 cells. both lines phosphorylation highly sensitive phosphatases, okadaic acid markedly stabilized phosphate incorporation. Phosphoamino analysis revealed that occurred predominantly on serine. Using site-directed mutagenesis we identified site at serine 129 within C-terminal domain α-synuclein. An additional site, which less efficiently, mapped 87. The located consensus recognition sequence casein kinase 1 (CK-1). vitro two-dimensional phosphopeptide mapping provided further evidence by CK-1 CK-2. Moreover, reducedin vivo upon inhibition or These data demonstrate is its C terminus may indicate function regulated phosphorylation/dephosphorylation.