Protein tyrosine phosphatase PTPRT as a regulator of synaptic formation and neuronal development
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PTPRT/RPTP 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.
Abstract
PTPRT/RPTP 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.
참고문헌 (42)
- Alonso A, "Protein tyrosine phosphatases in the human genome", Cell, 117, pp.699~711 (2004)
- Mustelin T, "Protein tyrosine phosphatases and the immune response", Nat Rev Immunol, 5, pp.43~57 (2005)
- Tonks NK, "Protein tyrosine phosphatases: from genes, to function, to disease", Nat Rev Mol Cell Biol, 7, pp.833~346 (2006)
- Lemmon MA, "Cell signaling by receptor-tyrosine kinases", Cell, 141, pp.1117~1134 (2010)
- Andersen JN, "A genomic perspective on protein tyrosine phosphatases: gene structure, pseudogenes, and genetic disease linkage", FASEB J, 18, pp.8~13 (2004)
- Besco JA, "Genomic organization and alternative splicing of the human and mouse RPTP genes", BMC Genomics, 2, pp.1~ (2001)
- Paul S, "Receptor and non-receptor protein tyrosine phosphatases in the nervous system", Cell Mol Life Sci, 60, pp.2465~2482 (2003)
- Dunah AW, "LAR receptor protein tyrosine phosphatases in the development and maintenance of excitatory synapses", Nat Neurosci, 8, pp.458~467 (2005)
- Woo J, "Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses", Nat Neurosci, 12, pp.428~437 (2009)
- Streuli M, "Expression of the receptor-linked protein tyrosine phosphatase LAR: proteolytic cleavage and shedding of the CAM-like extracellular region", EMBO J, 9, pp.2399~2407 (1990)
- Anders L, "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, pp.3917~3934 (2006)
- Lim SH, "Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn", EMBO J, 28, pp.3564~3578 (2009)
- Burden-Gulley SM, "PTPμ regulates N-cadherin-dependent neurite outgrowth", J Cell Biol, 144, pp.1323~1336 (1999)
- Burden-Gulley SM, "Protein tyrosine phophatase-μ differentially regulates neurite outgrowth of nasal and temporal neurons in the retina", J Neurosci, 22, pp.3615~3627 (2002)
- Johnson KG, "Receptor protein tyrosine phosphatases in nervous system development", Physiol Rev, 83, pp.1~24 (2003)
- McAndrew PE, "Identification and characterization of RPTP, a novel ", -like receptor protein tyrosine phosphatase whose expression is restricted to the central nervous system, 1998, pp.56, 9~21
- McAndrew PE, "Novel receptor protein tyrosine phosphatase(RPTP)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, pp.444~455 (1998)
- Besco J, "Genomic structure and alternative splicing of murine R2B receptor protein tyrosine phosphatases(PTP, , and PCP-2)", BMC Genomics, 5, pp.14~ (2004)
- Park AR, "Regulation of dendritic arborization by BCR Rac1 GTPase-activating protein, a substrate of PTPRT", J Cell Sci, 125, pp.4518~4531 (2012)
- Zondag GCM, "Homophilic interactions mediated by receptor tyrosine phosphatase and ", J Biol Chem, 270, pp.14247~14250 (1995)
- Aricescu AR, "Structure of a Tyrosine Phosphatase Adhesive Interaction Reveals a Spacer-Clamp Mechanism", Science, 317, pp.1217~1220 (2007)
- Chih B, "Control of excitatory and inhibitory synapse formation by neuroligins", Science, 307, pp.1324~1328 (2005)
- Boucard AA, "A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to α-and β-neurexins", Neuron, 48, pp.229~236 (2005)
- Lim SH, "PTPRT regulates the interaction of Syntaxin-binding protein 1 with Syntaxin 1through dephosphorylation of specific tyrosine residue", Biochem Biophys Res Comm, 439, pp.40~46 (2013)
- Rizo J, "SNAREs and Munc 18 in synaptic vesicle fusion", Nat Rev Neurosci, 3, pp.641~653 (2002)
- Deak F, "Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming", J Cell Biol, 184, pp.751~764 (2009)
- Li H, "Actin filament assembly by myristoylated, alanine-rich C kinase substratephosphatidylinositil-4, 5-diphosphate signaling is critical for dendrite branching", Mol Biol Cell, 19, pp.4804~4813 (2008)
- Luo L, "Actin cytoskeleton regulation in neuronal morphogenesis and structural plasticity", Annu Rev Cell Dev Biol, 18, pp.601~635 (2002)
- Chen H, "RhoA regulates dendritic branching in hippocampal neurons by decreasing cypin protein levels", J Neurosci, 27, pp.8378~8386 (2007)
- Nakayama AY, "Small GTPase Rac and Rho in the maintenance of dendritic spines and branches in hippocampal pyramidal neurons", J Neurosci, 20, pp.5329~5338 (2000)
- Luo L, "Rho GTPases in neuronal morphogenesis", Nat Rev Neurosci, 1, pp.173~180 (2000)
- Chuang TH, "Abr and Bcr are multifunctional regulators of the Rho GTP-binding protein gamily", Proc Natl Acad Sci U S A, 92, pp.10282~10286 (1995)
- Kweon SM, "Activity of the Bcr GTPase-activating domain is regulated through direct protein", protein interaction with the Rho guanine nucleotide dissociation inhibitor, 2008, pp.283, 3023~3030
- Oh D, "Regulation of synaptic Rac1 activity, long-term potentiation maintenance, and learning and memory by BCR and ABR Rac GTPase-activating proteins", J Neurosci, 30, pp.14134~14144 (2010)
- Turner CE, "Paxillin and focal adhesion signaling", Nat Cell Biol, 2, pp.231~236 (2000)
- Zhao Y, "Identification and functional characterization of paxillin as a target of protein tyrosine phosphatase receptor T", Proc Natl Acad Sci, 107, pp.2592~2597 (2010)
- Bilwes AM, "Novel Structural basis for inhibition of receptor protein-tyrosine phosphatase-α by dimerization", Nature, 382, pp.555~559 (1996)
- Xie Y, "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, pp.16482~16492 (2006)
- Wang Z, "Mutational analysis of the tyrosine phosphatome in colorectal cancers", Science, 304, pp.1164~1166 (2004)
- Schuurs-Hoeijmakers JH, "Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing", J Med Genet, 50, pp.802~811 (2013)
- Allen-Brady K, "A highdensity SNP genome-wide linkage scan in a large autism extended pedigree", Mol Psych, 14, pp.590~600 (2009)
- Rajamani KT, "Inactivation of the catalytic phosphatase domain of PTPRT", RPTP increases social interaction in mice, 2014, ~