Neuropsin—A possible modulator of synaptic plasticity

Shiosaka, Sadao; Ishikawa, Yasuyuki

doi:10.1016/j.jchemneu.2011.05.014

Cited by 45 publications

(38 citation statements)

References 62 publications

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“…Neural activity-dependent processing of extracellular proteins, particularly in the synaptic cleft, is of pivotal importance for the function of molecules such as neurotrophic factors, matrix proteins, cell adhesion molecules, and receptor extracellular domains, and has implications for cell migration, neurite outgrowth, synaptogenesis, neural plasticity, and neurite retraction (Lu, 2003;Reiss and Saftig, 2009;Dityatev et al, 2010;Shiosaka and Ishikawa, 2011). However, the target molecules for proteases remain to be identified, primarily due to difficulties in determining specific substrate-enzyme interactions (Ló pez-Otín and Overall, 2002).…”

Section: Introductionmentioning

confidence: 99%

Processing of Neuregulin-1 by Neuropsin Regulates GABAergic Neuron to Control Neural Plasticity of the Mouse Hippocampus

et al. 2012

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Protease-mediated signaling is an important modulator of the nervous system. However, identifying the specific signaling substrates of such proteases is limited by the rapidity with which intermediate substrate forms are cleaved and released. Here, a screening method to detect noncleaved enzyme-bound forms was developed and used to identify a novel neuropsin/neuregulin-1 (NRG-1) proteolytic signaling system, which is specifically localized in the microdomain of synaptic cleft, in the mouse hippocampus. The extracellular protease, neuropsin, cleaved mature NRG-1 (comprising the extracellular domain of the NRG-1) at three newly identified sites to remove the heparin-binding domain of NRG-1. This released the ligand moiety from the matrix-glycosaminoglycan pool and enabled it to trigger the phosphorylation of NRG-1 receptor, p185 (ErbB4). Proteolysis of mature NRG-1 by neuropsin led to colocalization of the processed NRG-1 with ErbB4 in parvalbumin-positive hippocampal interneurons and consequent phosphorylation of tyrosine residues of proteins in the cells. Moreover, neuropsin knock-out mice exhibited impairments in Schaffer collateral early phase long-term potentiation, and application of the recombinant NRG-1 lacking heparin-binding activity reversed the effects through the activation of ErbB4 and GABA A receptors. Thus, ErbB4 signaling induced by neuropsin-dependent processing of NRG-1 contributes to the modulation of synaptic plasticity via regulation of GABAergic transmission. This signaling system may be involved in human cognition and mental disorders, such as schizophrenia and bipolar disorder, by its dysfunction.

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Section: Introductionmentioning

confidence: 99%

Processing of Neuregulin-1 by Neuropsin Regulates GABAergic Neuron to Control Neural Plasticity of the Mouse Hippocampus

et al. 2012

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“…Chemical fluorescence imaging for Neuropsin activity in hippocampus of the freely-moving mouse Neuropsin (NP) and tissue plasminogen activator are a highly specific serine proteases expressed in the hippocampus during events that require synaptic plasticity, and play a crucial role in neuronal hyper excitability induced by epileptogenic insult [10]. The spatial and temporal dynamics of these proteins activity are therefore likely to be important in determining the behavioral correlates of seizures.…”

Section: Resultsmentioning

confidence: 99%

Functional neuroimaging by using an implantable CMOS multimodal device in a freely-moving mouse

Kobayashi

Tamura

Hatanaka

et al. 2011

2011 IEEE Biomedical Circuits and Systems Conference (BioCAS)

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We have developed implantable complementary metal oxide semiconductor (CMOS) multimodal devices to observe various neural activities in the brain. The devices, biomedical photonic large scale integration (BpLSI), have an image sensing array, light emitting diodes (LEDs), and an absorbing filter to enable a real-time fluorescence imaging. Additionally, BpLSI can equip with electrodes, a cannula, and an optical fiber for various applications. Here, we report three applications of BpLSI for freely-moving mice to visualize serine-protease activities in the hippocampus, to monitor kinetic alterations of dopaminergic-fibers in the striatum, and to obtain physiological responses with broad scope in the visual cortex.

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“…Since neuropsin deficiency completely inhibits the early phase of LTP, associations of Neuropsin between early and persistent-LTP synapses are speculated to be related to mammalian working memory and consequently integration in learning and memory. 145 A recent report shows that neuropsin in the mouse brain is important for stress-related plasticity in the amygdala (a region involved in processing emotions). 146 Stress initiates neuropsindependent cleavage of EphB2 in the amygdala, resulting in dissociation of EphB2 from the NR1 subunit of the NMDA receptor, thus inducing membrane turnover of EphB2 receptors.…”

Section: Neuropsinmentioning

confidence: 99%

The role of proteases in regulating Eph/ephrin signaling

Atapattu

Lackmann²,

Janes³

2014

Cell Adhesion & Migration

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Proteases regulate a myriad of cell functions, both in normal and disease states. In addition to protein turnover, they regulate a range of signaling processes, including those mediated by Eph receptors and their ephrin ligands. A variety of proteases is reported to directly cleave Ephs and/or ephrins under different conditions, to promote receptor and/or ligand shedding, and regulate receptor/ligand internalisation and signaling. They also cleave other adhesion proteins in response to Eph-ephrin interactions, to indirectly facilitate Eph-mediated functions. Proteases thus contribute to Eph/ ephrin mediated changes in cell-cell and cell-matrix interactions, in cell morphology and in cell migration and invasion, in a manner which appears to be tightly regulated by, and co-ordinated with, Eph signaling. This review summarizes the current literature describing the function and regulation of protease activities during Eph/ephrin-mediated cell signaling.

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Neuropsin—A possible modulator of synaptic plasticity

Cited by 45 publications

References 62 publications

Processing of Neuregulin-1 by Neuropsin Regulates GABAergic Neuron to Control Neural Plasticity of the Mouse Hippocampus

Processing of Neuregulin-1 by Neuropsin Regulates GABAergic Neuron to Control Neural Plasticity of the Mouse Hippocampus

Functional neuroimaging by using an implantable CMOS multimodal device in a freely-moving mouse

The role of proteases in regulating Eph/ephrin signaling

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