title: PTPRT regulates the interaction of Syntaxin-binding protein 1 with Syntaxin 1 through dephosphorylation of specific tyrosine residue.
abstract: 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.
authors: Biomedical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors: So-Hee
authors: SH
authors: Lim
authors: Jeonghee
authors: J
authors: Moon
authors: Myungkyu
authors: M
authors: Lee
authors: Jae-Ran
authors: JR
authors: Lee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051938:Munc18 Proteins / Q000378:metabolism*; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000378:metabolism*; D050600:SNARE Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D051938:Munc18 Proteins; D050600:SNARE Proteins; C497937:STXBP1 protein, human; C497939:Stxbp1 protein, rat; D014443:Tyrosine; C516865:PTPRT protein, human; C584314:PTPRT protein, rat; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: PTPRT; SNARE complex; Synaptic vesicle fusion; Syntaxin-binding protein 1