PTPRT regulates the interaction of Syntaxin-binding protein 1 with Syntaxin 1 through dephosphorylation of specific tyrosine residue.
PTPRT (protein tyrosine phosphatase receptor T), a brain-specific tyrosine phosphatase, has been found to regulate synaptic formation and development of hippocampal neurons, but its regulation mechanism is not yet fully understood. Here, Syntaxin-binding protein 1, a key component of synaptic vesicle fusion machinery, was identified as a possible interaction partner ... and an endogenous substrate of PTPRT. PTPRT interacted with Syntaxin-binding protein 1 in rat synaptosome, and co-localized with Syntaxin-binding protein 1 in cultured hippocampal neurons. PTPRT dephosphorylated tyrosine 145 located around the linker between domain 1 and 2 of Syntaxin-binding protein 1. Syntaxin-binding protein 1 directly binds to Syntaxin 1, a t-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein, and plays a role as catalysts of SNARE complex formation. Syntaxin-binding protein 1 mutant mimicking non-phosphorylation (Y145F) enhanced the interaction with Syntaxin 1 compared to wild type, and therefore, dephosphorylation of Syntaxin-binding protein 1 appeared to be important for SNARE-complex formation. In conclusion, PTPRT could regulate the interaction of Syntaxin-binding protein 1 with Syntaxin 1, and as a result, the synaptic vesicle fusion appeared to be controlled through dephosphorylation of Syntaxin-binding protein 1.
Mesh Terms:
Animals, Cells, Cultured, Cloning, Molecular, HEK293 Cells, Hippocampus, Humans, Munc18 Proteins, Mutation, Neurons, Phosphorylation, Protein Binding, Protein Tyrosine Phosphatases, Rats, Receptor-Like Protein Tyrosine Phosphatases, Class 2, SNARE Proteins, Substrate Specificity, Tyrosine
Animals, Cells, Cultured, Cloning, Molecular, HEK293 Cells, Hippocampus, Humans, Munc18 Proteins, Mutation, Neurons, Phosphorylation, Protein Binding, Protein Tyrosine Phosphatases, Rats, Receptor-Like Protein Tyrosine Phosphatases, Class 2, SNARE Proteins, Substrate Specificity, Tyrosine
Biochem. Biophys. Res. Commun.
Date: Sep. 13, 2013
PubMed ID: 23962429
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