Hyperpolarization-activated cation current Ih of dentate gyrus granule cells is upregulated in human and rat temporal lobe epilepsy |
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Authors: | Surges Rainer Kukley Maria Brewster Amy Rüschenschmidt Christiane Schramm Johannes Baram Tallie Z Beck Heinz Dietrich Dirk |
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Institution: | Department of Biological Chemistry and CNR Institute of Neurosciences, University of Padova, V.le G. Colombo 3, 35131 Padova, Italy. |
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Abstract: | Phosphorylation of α-synuclein at Ser-129 is of crucial relevance to Parkinson's disease and related synucleinopathies. Here we provide biochemical evidence that PLK2 and to a lesser extent PLK3 are superior over CK2, as catalysts of Ser-129 phosphorylation both in full length α-synuclein and in a peptide reproducing the C-terminal segment of the protein. By using substituted peptides we also show that the sequence surrounding Ser-129 is optimally shaped for undergoing phosphorylation by PLK2, with special reference to the two acidic residues at positions n-3 (Glu-126) and n+2 (Glu-131) whose replacement with alanine abrogates phosphorylation. |
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