• 생물정신의학
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• 제17권3호
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• pp.119-126
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• 2010

Synaptic adhesion molecules mediate synapse formation, maturation and maintenance. These proteins are localized at synaptic sites in neuronal axons and dendrites. These proteins function as a bridge of synaptic cleft via interaction with another synaptic adhesion molecules in the opposite side. They can interact with scaffold proteins via intracellular domain and recruit many synaptic proteins, signaling proteins and synaptic vesicles. Scaffold proteins function as a platform in dendritic spines or axonal terminals. Recently, many genetic studies have revealed that synaptic adhesion molecules and scaffold proteins are important in neurodevelopmental disorders, psychotic disorders, mood disorders and anxiety disorders. In this review, fundamental mechanisms of synapse formation and maturation related with synaptic adhesion molecules and scaffold proteins are introduced and their psychiatric implications addressed.

• Molecules and Cells
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• 제41권7호
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• pp.622-630
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• 2018

Leukocyte common antigen-related protein tyrosine phosphatases (LAR-RPTPs) are cellular receptors of heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans that regulate neurite outgrowth and neuronal regeneration. LAR-RPTPs have also received particular attention as the major presynaptic hubs for synapse organization through selective binding to numerous postsynaptic adhesion partners. Recent structural studies on LAR-RPTP-mediated trans-synaptic adhesion complexes have provided significant insight into the molecular basis of their specific interactions, the key codes for their selective binding, as well as the higher-order clustering of LAR-RPTPs necessary for synaptogenic activity. In this review, we summarize the structures of LAR-RPTPs in complex with various postsynaptic adhesion partners and discuss the molecular mechanisms underlying LAR-RPTP-mediated synaptogenesis.

• BMB Reports
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• 제48권5호
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• pp.249-255
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• 2015

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]

• Molecules and Cells
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• 제39권10호
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• pp.762-767
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• 2016

Fasciclin II (FasII), the Drosophila ortholog of neural cell adhesion molecule (NCAM), plays a critical role in synaptic stabilization and plasticity. Although this molecule undergoes constitutive cycling at the synaptic membrane, how its membrane trafficking is regulated to ensure proper synaptic development remains poorly understood. In a genetic screen, we recovered a mutation in Drosophila mical-like that displays an increase in bouton numbers and a decrease in FasII levels at the neuromuscular junction (NMJ). Similar phenotypes were induced by presynaptic, but not postsynaptic, knockdown of mical-like expression. FasII trafficking assays revealed that the recycling of internalized FasII molecules to the cell surface was significantly impaired in mical-like-knockdown cells. Importantly, this defect correlated with an enhancement of endosomal sorting of FasII to the lysosomal degradation pathway. Similarly, synaptic vesicle exocytosis was also impaired in mical-like mutants. Together, our results identify Mical-like as a novel regulator of synaptic growth and FasII endocytic recycling.

• Molecules and Cells
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• 제41권5호
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• pp.373-380
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• 2018

Synapses and neural circuits form with exquisite specificity during brain development to allow the precise and appropriate flow of neural information. Although this property of synapses and neural circuits has been extensively investigated for more than a century, molecular mechanisms underlying this property are only recently being unveiled. Recent studies highlight several classes of cell-surface proteins as organizing hubs in building structural and functional architectures of specific synapses and neural circuits. In the present minireview, we discuss recent findings on various synapse organizers that confer the distinct properties of specific synapse types and neural circuit architectures in mammalian brains, with a particular focus on the hippocampus and cerebellum.