Peroxynitrite induces tyrosine residue modifications in synaptophysin C-terminal domain, affecting its interaction with src. Journal of neurochemistry [J Neurochem] Journal article | | Title | Peroxynitrite induces tyrosine residue modifications in synaptophysin C-terminal domain, affecting its interaction with src. | | Author(s) | Mallozzi C, Ceccarini M, Camerini S, Macchia G, Crescenzi M, Petrucci TC, Di Stasi AM | | Institution | Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299 - 00161 Rome (Italy). | | Source | J Neurochem 2009 Sep 8. | | Abstract | Abstract Peroxynitrite is a potent oxidant that contributes to tissue damage in neurodegenerative disorders. We have previously reported that treatment of rat brain synaptosomes with peroxynitrite induced post-translational modifications in pre- and post-synaptic proteins and stimulated SNARE complex formation and endogenous glutamate release. In this study we show that, following peroxynitrite treatment, the synaptic vesicle protein synaptophysin can be both phosphorylated and nitrated in a dose-dependent manner. We found that tyrosine-phosphorylated, but not tyrosine-nitrated, synaptophysin bound to the src tyrosine kinase and enhanced its catalytic activity. These effects were mediated by direct and specific binding of the synaptophysin cytoplasmic C-terminal tail with the src-SH2 domain. Using mass spectrometry analysis, we mapped the synaptophysin C-terminal tail tyrosine residues modified by peroxynitrite and found one nitration site at Tyr(250) and two phosphorylation sites at Tyr(263) and Tyr(273). We suggest that peroxynitrite-mediated modifications of synaptophysin may be relevant in modulating src signalling of synaptic terminal in pathophysiological conditions. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19737347 |
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