Advanced SearchSearch Tips
Protein tyrosine phosphatase PTPRT as a regulator of synaptic formation and neuronal development
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : BMB Reports
  • Volume 48, Issue 5,  2015, pp.249-255
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2015.48.5.037
 Title & Authors
Protein tyrosine phosphatase PTPRT as a regulator of synaptic formation and neuronal development
Lee, Jae-Ran;
  PDF(new window)
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]
PTPRT;Receptor-type protein tyrosine phosphatase;Neuronal synapse formation;Dendritic arborization;Neuronal development;
 Cited by
Copy number variation analysis of patients with intellectual disability from North-West Spain, Gene, 2017, 626, 189  crossref(new windwow)
Rho GTPase-activating proteins: Regulators of Rho GTPase activity in neuronal development and CNS diseases, Molecular and Cellular Neuroscience, 2017, 80, 18  crossref(new windwow)
Alonso A, Sasin J, Bottini N et al (2004) Protein tyrosine phosphatases in the human genome. Cell 117, 699-711 crossref(new window)

Mustelin T, Vang T and Bottini N (2005) Protein tyrosine phosphatases and the immune response. Nat Rev Immunol 5, 43-57 crossref(new window)

Tonks NK (2006) Protein tyrosine phosphatases: from genes, to function, to disease. Nat Rev Mol Cell Biol 7, 833-346 crossref(new window)

Lemmon MA and Schlessinger J (2010) Cell signaling by receptor-tyrosine kinases. Cell 141, 1117-1134 crossref(new window)

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 crossref(new window)

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 crossref(new window)

Paul S and Lombroso PJ (2003) Receptor and non-receptor protein tyrosine phosphatases in the nervous system. Cell Mol Life Sci 60, 2465-2482 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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

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 crossref(new window)

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 crossref(new window)

Burden-Gulley SM and Brady-Kalnay SM (1999) PTPμ regulates N-cadherin-dependent neurite outgrowth. J Cell Biol 144, 1323-1336 crossref(new window)

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

Johnson KG and Van Vactor D (2003) Receptor protein tyrosine phosphatases in nervous system development. Physiol Rev 83, 1-24 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

Chih B, Engelman H and Scheiffele P (2005) Control of excitatory and inhibitory synapse formation by neuroligins. Science 307, 1324-1328 crossref(new window)

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 crossref(new window)

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 crossref(new window)

Rizo J and Sudhof TC (2002) SNAREs and Munc 18 in synaptic vesicle fusion. Nat Rev Neurosci 3, 641-653 crossref(new window)

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 crossref(new window)

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 crossref(new window)

Luo L (2002) Actin cytoskeleton regulation in neuronal morphogenesis and structural plasticity. Annu Rev Cell Dev Biol 18, 601-635 crossref(new window)

Chen H and Firestein BL (2007) RhoA regulates dendritic branching in hippocampal neurons by decreasing cypin protein levels. J Neurosci 27, 8378-8386 crossref(new window)

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

Luo L (2000) Rho GTPases in neuronal morphogenesis. Nat Rev Neurosci 1, 173-180 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

Turner CE (2000) Paxillin and focal adhesion signaling. Nat Cell Biol 2.E231-E236 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

Wang Z, Shen D, Parsons DW et al (2004) Mutational analysis of the tyrosine phosphatome in colorectal cancers. Science 304, 1164-1166 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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] crossref(new window)