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http://dx.doi.org/10.5483/BMBRep.2015.48.5.037

Protein tyrosine phosphatase PTPRT as a regulator of synaptic formation and neuronal development  

Lee, Jae-Ran (Biomedical Translational Research Center, Korea Research Institute of Bioscience & Biotechnology)
Publication Information
BMB Reports / v.48, no.5, 2015 , pp. 249-255 More about this Journal
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. [BMB Reports 2015; 48(5): 249-255]
Keywords
PTPRT; Receptor-type protein tyrosine phosphatase; Neuronal synapse formation; Dendritic arborization; Neuronal development;
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1 Alonso A, Sasin J, Bottini N et al (2004) Protein tyrosine phosphatases in the human genome. Cell 117, 699-711   DOI   ScienceOn
2 Mustelin T, Vang T and Bottini N (2005) Protein tyrosine phosphatases and the immune response. Nat Rev Immunol 5, 43-57   DOI   ScienceOn
3 Tonks NK (2006) Protein tyrosine phosphatases: from genes, to function, to disease. Nat Rev Mol Cell Biol 7, 833-346   DOI   ScienceOn
4 Lemmon MA and Schlessinger J (2010) Cell signaling by receptor-tyrosine kinases. Cell 141, 1117-1134   DOI   ScienceOn
5 Dunah AW, Hueske E, Wyszynski M et al (2005) LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses. Nat Neurosci 8, 458-467   DOI
6 Andersen JN, Jansen PG, Echwald SM et al (2004) A genomic perspective on protein tyrosine phosphatases: gene structure, pseudogenes, and genetic disease linkage. FASEB J 18, 8-13   DOI   ScienceOn
7 Besco JA, Frostholm A, Popesco MC et al (2001) Genomic organization and alternative splicing of the human and mouse RPTPρ genes. BMC Genomics 2, 1   DOI
8 Paul S and Lombroso PJ (2003) Receptor and non-receptor protein tyrosine phosphatases in the nervous system. Cell Mol Life Sci 60, 2465-2482   DOI
9 Woo J, Kwon SK, Choi S et al (2009) Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses. Nat Neurosci 12, 428-437   DOI   ScienceOn
10 Streuli M, Krueger NX, Ariniello PD et al (1990) Expression of the receptor-linked protein tyrosine phosphatase LAR: proteolytic cleavage and shedding of the CAM-like extracellular region. EMBO J 9, 2399-2407
11 Anders L, Mertins P, Lammich S et al (2006) Furin-, ADAM 10-, and γ-secretase-mediated cleavage of a receptor tyrosine phosphatase and regulation of β-catenin’s transcriptional activity. Mol Cell Biol 26, 3917-3934   DOI   ScienceOn
12 Lim SH, Kwon SK, Lee MK et al (2009) Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn. EMBO J 28, 3564-3578   DOI   ScienceOn
13 Burden-Gulley SM and Brady-Kalnay SM (1999) PTPμ regulates N-cadherin-dependent neurite outgrowth. J Cell Biol 144, 1323-1336   DOI   ScienceOn
14 McAndrew PE, Frostholm A, Evans JE et al (1998) Novel receptor protein tyrosine phosphatase (RPTPρ) and acidic fibroblast growth factor (FGF-1) transcripts delineate a rostrocaudal boundary in the granule cell of the murine cerebellar cortex. J Comp Neurol 391, 444-455   DOI
15 Burden-Gulley SM, Ensslen SE and Brady-Kalnay SM (2002) Protein tyrosine phophatase-μ differentially regulates neurite outgrowth of nasal and temporal neurons in the retina. J Neurosci 22, 3615-3627
16 Johnson KG and Van Vactor D (2003) Receptor protein tyrosine phosphatases in nervous system development. Physiol Rev 83, 1-24   DOI   ScienceOn
17 Zondag GCM, Koningstein GM, Jiang YP et al (1995) Homophilic interactions mediated by receptor tyrosine phosphatase μ and κ. J Biol Chem 270, 14247-14250   DOI   ScienceOn
18 McAndrew PE, Frostholm A, White R et al (1998) Identification and characterization of RPTPρ, a novel μ/κ -like receptor protein tyrosine phosphatase whose expression is restricted to the central nervous system. Mol Brain Res 56, 9-21   DOI   ScienceOn
19 Besco J, Popesco MC, Davuluri RV et al (2004) Genomic structure and alternative splicing of murine R2B receptor protein tyrosine phosphatases (PTPκ, μ, ρ and PCP-2). BMC Genomics 5, 14   DOI   ScienceOn
20 Park AR, Oh D, Lim SH et al (2012) Regulation of dendritic arborization by BCR Rac1 GTPase-activating protein, a substrate of PTPRT. J Cell Sci 125, 4518-4531   DOI   ScienceOn
21 Aricescu AR, Siebold C, Choudhuri K et al (2007) Structure of a Tyrosine Phosphatase Adhesive Interaction Reveals a Spacer-Clamp Mechanism. Science 317, 1217-1220   DOI   ScienceOn
22 Chih B, Engelman H and Scheiffele P (2005) Control of excitatory and inhibitory synapse formation by neuroligins. Science 307, 1324-1328   DOI   ScienceOn
23 Deak F, Xu Y, Chang WP et al (2009) Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming. J Cell Biol 184, 751-764   DOI   ScienceOn
24 Boucard AA, Chubykin AA, Comoletti D et al (2005) A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to α-and β-neurexins. Neuron 48, 229-236   DOI   ScienceOn
25 Lim SH, Moon J, Lee M et al (2013) PTPRT regulates the interaction of Syntaxin-binding protein 1 with Syntaxin 1 through dephosphorylation of specific tyrosine residue. Biochem Biophys Res Comm 439, 40-46   DOI   ScienceOn
26 Chen H and Firestein BL (2007) RhoA regulates dendritic branching in hippocampal neurons by decreasing cypin protein levels. J Neurosci 27, 8378-8386   DOI   ScienceOn
27 Rizo J and Sudhof TC (2002) SNAREs and Munc 18 in synaptic vesicle fusion. Nat Rev Neurosci 3, 641-653   DOI   ScienceOn
28 Li H, Chen G, Zhou B et al (2008) Actin filament assembly by myristoylated, alanine-rich C kinase substratephosphatidylinositil-4,5-diphosphate signaling is critical for dendrite branching. Mol Biol Cell 19, 4804-4813   DOI
29 Luo L (2002) Actin cytoskeleton regulation in neuronal morphogenesis and structural plasticity. Annu Rev Cell Dev Biol 18, 601-635   DOI   ScienceOn
30 Nakayama AY, Harms MB and Luo L (2000) Small GTPase Rac and Rho in the maintenance of dendritic spines and branches in hippocampal pyramidal neurons. J Neurosci 20, 5329-5338
31 Luo L (2000) Rho GTPases in neuronal morphogenesis. Nat Rev Neurosci 1, 173-180   DOI
32 Chuang TH, Xu X, Kaartinen V et al (1995) Abr and Bcr are multifunctional regulators of the Rho GTP-binding protein gamily. Proc Natl Acad Sci U S A 92, 10282-10286   DOI
33 Zhao Y, Zhang X, Gudac K et al (2010) Identification and functional characterization of paxillin as a target of protein tyrosine phosphatase receptor T. Proc Natl Acad Sci 107, 2592-2597   DOI   ScienceOn
34 Kweon SM, Cho YJ, Minoo P et al (2008) Activity of the Bcr GTPase-activating domain is regulated through direct protein/protein interaction with the Rho guanine nucleotide dissociation inhibitor. J Biol Chem 283, 3023-3030   DOI   ScienceOn
35 Xie Y, Massa SM, Ensslen-Craig SE et al (2006) Protein-tyrosine Phosphatase (PTP) Wedge Domain Peptides: a novel approach for inhibition of PTP function and augmentation of protein-tyrosine kinase function. J Biol Chem 281, 16482-16492   DOI   ScienceOn
36 Oh D, Han S and Seo J et al (2010) Regulation of synaptic Rac1 activity, long-term potentiation maintenance, and learning and memory by BCR and ABR Rac GTPase-activating proteins. J Neurosci 30, 14134-14144   DOI   ScienceOn
37 Turner CE (2000) Paxillin and focal adhesion signaling. Nat Cell Biol 2.E231-E236   DOI   ScienceOn
38 Bilwes AM, Hertog J, Hunter T et al (1996) Novel Structural basis for inhibition of receptor protein-tyrosine phosphatase-α by dimerization. Nature 382, 555-559   DOI   ScienceOn
39 Wang Z, Shen D, Parsons DW et al (2004) Mutational analysis of the tyrosine phosphatome in colorectal cancers. Science 304, 1164-1166   DOI   ScienceOn
40 Schuurs-Hoeijmakers JH, Vulto-van Silfhout AT, Vissers LEL et al (2013) Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing. J Med Genet 50, 802-811   DOI   ScienceOn
41 Allen-Brady K, Miller J, Matsunami N et al (2009) A highdensity SNP genome-wide linkage scan in a large autism extended pedigree. Mol Psych 14, 590-600   DOI   ScienceOn
42 Rajamani KT, O’Neill B, Han DD et al (2014) Inactivation of the catalytic phosphatase domain of PTPRT/RPTPρ increases social interaction in mice. Autism Res doi: 10.1002/aur.1390 [Epub ahead of print]   DOI   ScienceOn