BMB Rep. 2015; 48(5): 249-255  
Protein tyrosine phosphatase PTPRT as a regulator of synaptic formation and neuronal development
Jae-Ran Lee*
Biomedical Translational Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon 305-806, Korea
Correspondence to: Tel: +82-42-879-8437; Fax: +82-42-879-8596; E-mail: leejr@kribb.re.kr
Received: February 25, 2015; Published online: May 31, 2015.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

Abstract
PTPRT/RPTPρ is the most recently isolated member of the type IIB receptor-type protein tyrosine phosphatase family and its expression is restricted to the nervous system. PTPRT plays a critical role in regulation of synaptic formation and neuronal development. When PTPRT was overexpressed in hippocampal neurons, synaptic formation and dendritic arborization were induced. On the other hand, knockdown of PTPRT decreased neuronal transmission and attenuated neuronal development. PTPRT strengthened neuronal synapses by forming homophilic trans dimers with each other and heterophilic cis complexes with neuronal adhesion molecules. Fyn tyrosine kinase regulated PTPRT activity through phosphorylation of tyrosine 912 within the membrane-proximal catalytic domain of PTPRT. Phosphorylation induced homophilic cis dimerization of PTPRT and resulted in the inhibition of phosphatase activity. BCR-Rac1 GAP and Syntaxin-binding protein were found as new endogenous substrates of PTPRT in rat brain. PTPRT induced polymerization of actin cytoskeleton that determined the morphologies of dendrites and spines by inhibiting BCR-Rac1 GAP activity. Additionally, PTPRT appeared to regulate neurotransmitter release through reinforcement of interactions between Syntaxin-binding protein and Syntaxin, a SNARE protein. In conclusion, PTPRT regulates synaptic function and neuronal development through interactions with neuronal adhesion molecules and the dephosphorylation of synaptic molecules.
Keywords: PTPRT, Receptor-type protein tyrosine phosphatase, Neuronal synapse formation, Dendritic arborization, Neuronal development


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