Ephrin-A5 and EphA5 Interaction Induces Synaptogenesis during Early Hippocampal Development

Akaneya, Yukio; Sohya, Kazuhiro; Kitamura, Akihiko; Kimura, Fumitaka; Washburn, Chris; Zhou, Ran; Ninan, Ipe; Tsumoto, Tadaharu; Ziff, Edward B.

doi:10.1371/journal.pone.0012486

Cited by 64 publications

(55 citation statements)

References 72 publications

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“…EGTA is a calcium chelator, and by using EGTA to chelate the calcium in the culture system, the increase in cytoplasmic calcium concentrations and the upregulation of Ephrin-A4 after OGD/R was alleviated ( Figure 3B and 3C), indicating the significance of calcium overloading for the upregulation of Ephrin-A4. It was reported that the expression of Ephrin-A4 was more likely mediated by the CaMKII/CREB signaling pathway [24] . Then, we determined the translocation of CREB into the nucleus.…”

Section: Wwwchinapharcom Wu Ly Et Almentioning

confidence: 99%

Connexin 43 stabilizes astrocytes in a stroke-like milieu to facilitate neuronal recovery

Feng

2015

Acta Pharmacol Sin

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Aim: Connexin 43 (Cx43) is a member of connexin family mainly expressed in astrocytes, which forms gap junctions and hemichannels and maintains the normal shape and function of astrocytes. In this study we investigated the role of Cx43 in astrocytes in facilitating neuronal recovery during ischemic stroke. Methods: Primary culture of astrocytes or a mixed culture of astrocytes and cortical neurons was subjected to oxygen glucose deprivation and reperfusion (OGD/R). The expression of Cx43 and Ephrin-A4 in astrocytes was detected using immunocytochemical staining and Western blot assays. Intercellular Ca 2+ concentration was determined with Fluo-4 AM fluorescent staining. Middle cerebral artery occlusion (MCAO) model rats were used for in vivo studies. Results: OGD/R treatment of cultured astrocytes caused a decrement of Cx43 expression and translocation of Cx43 from cell membrane to cytoplasm, accompanied by cell retraction. Furthermore, OGD/R increased intracellular Ca 2+ concentration, activated CaMKII/CREB pathways and upregulated expression of Ephrin-A4 in the astrocytes. All these changes in OGD/R-treated astrocytes were alleviated by overexpression of Cx43. In the cortical neurons cultured with astrocytes, OGD/R inhibited the neurite growth, whereas overexpression of Cx43 or knockdown of Ephrin-A4 in astrocytes restored the neurite growth. In MCAO model rats, neuronal recovery was found to be correlated with the recuperation of Cx43 and Ephrin-A4 in astrocytes. Conclusion: Cx43 can stabilize astrocytes and facilitate the resistance to the deleterious effects of a stroke-like milieu and promote neuronal recovery.

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Section: Wwwchinapharcom Wu Ly Et Almentioning

confidence: 99%

Connexin 43 stabilizes astrocytes in a stroke-like milieu to facilitate neuronal recovery

Feng

2015

Acta Pharmacol Sin

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“…EphA4, EphA5, EphA6, and EphA7 are present in neurons during synapse formation and continue to be expressed by neuronal populations of the adult rodent brain (Buchert et al, 1999;Ciossek et al, 1999;Cooper et al, 2009;Galimberti et al, 2010;Grunwald et al, 2001;Liebl et al, 2003;Maisonpierre et al, 1993;Valenzuela et al, 1995). During synaptogenesis, EphA5 promotes transcriptional and signaling events involved in the early stages of this process (Akaneya et al, 2010). As neurons mature, EphA receptors become prominent in subcellular compartments of neurons, including presynaptic and postsynaptic terminals (Bouvier et al, 2008;Buchert et al, 1999;Tremblay et al, 2007).…”

Section: Localization Of Eph Receptors and Ephrins At Synapsesmentioning

confidence: 99%

Eph receptors and ephrins in neuron–astrocyte communication at synapses

Murai

Pasquale

2011

Glia

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Neuron-glia communication is essential for regulating the properties of synaptic connections in the brain. Astrocytes, in particular, play a critical and complex role in synapse development, maintenance, and plasticity. Likewise, neurons reciprocally influence astrocyte physiology. However, the molecular signaling events that enable astrocytes and neurons to effectively communicate with each other are only partially defined. Recent findings have revealed that Eph receptor tyrosine kinases and ephrins play an important role in contact-dependent neuron-glia communication at synapses. Upon binding, these two families of cell surface-associated proteins trigger bidirectional signaling events that regulate the structural and physiological properties of both neurons and astrocytes. This review will focus on the emerging role of Eph receptors and ephrins in neuron-astrocyte interaction at synapses and discuss implications for synaptic plasticity, behavior, and disease.

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“…EphBs have established roles in the formation of synapses, transforming dendritic filopodia to spines and clustering and phosphorylating Nmethyl-D-aspartate receptors (NMDARs) (7,9,23), and are implicated in synaptic plasticity, modulating NMDAR function (16). Less is known about the role of EphAs, although evidence suggests that they contribute to the induction of synaptogenesis (24), spine morphology, maturation, and collapse (25,26). EphA signaling alters the stability of synaptic boutons, modulating synaptic plasticity and regulating adhesion to the extracellular matrix (27) and the reorganization of the cytoskeleton (28).…”

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Activation of EphA Receptors Mediates the Recruitment of the Adaptor Protein Slap, Contributing to the Downregulation ofN-Methyl-d-Aspartate Receptors

Semerdjieva

Abdul-Razak

Salim

et al. 2013

Molecular and Cellular Biology

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bRegulation of the activity of N-methyl-D-aspartate receptors (NMDARs) at glutamatergic synapses is essential for certain forms of synaptic plasticity underlying learning and memory and is also associated with neurotoxicity and neurodegenerative diseases. In this report, we investigate the role of Src-like adaptor protein (Slap) in NMDA receptor signaling. We present data showing that in dissociated neuronal cultures, activation of ephrin (Eph) receptors by chimeric preclustered eph-Fc ligands leads to recruitment of Slap and NMDA receptors at the sites of Eph receptor activation. Interestingly, our data suggest that prolonged activation of EphA receptors is as efficient in recruiting Slap and NMDA receptors as prolonged activation of EphB receptors. Using established heterologous systems, we examined whether Slap is an integral part of NMDA receptor signaling. Our results showed that Slap does not alter baseline activity of NMDA receptors and does not affect Src-dependent potentiation of NMDA receptor currents in Xenopus oocytes. We also demonstrate that Slap reduces excitotoxic cell death triggered by activation of NMDARs in HEK293 cells. Finally, we present evidence showing reduced levels of NMDA receptors in the presence of Slap occurring in an activity-dependent manner, suggesting that Slap is part of a mechanism that homeostatically modulates the levels of NMDA receptors. In an effort to identify genes involved in cortical development, we have previously cloned slap, which encodes a Src-like adaptor protein (Slap) (1). slap is expressed strongly in the forebrain, but its function there remains unknown. slap encodes a 34-kDa protein containing SH2 and SH3 domains followed by a unique 104-amino-acid COOH terminal. Similar to results seen with members of the Src family kinases (SFKs), myristoylation at the NH2 terminus targets Slap to cellular membranes (2). Slap has been studied in the immune system, where it inhibits T-cell receptor (TCR) signaling (3) and is involved in the internalization and degradation of the TCR subunit (4). Furthermore, Slap abrogates the mitogenic response to platelet-derived growth factors (PDGFs) in NIH 3T3 fibroblasts, antagonizing the mitotic activity of Src kinase (5).Slap was initially identified in a yeast two-hybrid screen using the cytoplasmic tail of EphrinA2 as bait (6). Ephrin (Eph) receptors constitute the largest known family of receptor tyrosine kinases and, together with their membrane-bound ligands (eph ligands), have been implicated in a variety of patterning events during the development of the central nervous system (7-21). Ephs and their ligands act as contact-dependent adhesive molecules and are implicated in the development and function of synapses. They are divided into two classes (EphA and EphB), based on sequence homologies and binding specificity (22). EphBs have established roles in the formation of synapses, transforming dendritic filopodia to spines and clustering and phosphorylating Nmethyl-D-aspartate receptors (NMDARs) (7,9,23), and are implicated in...

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Ephrin-A5 and EphA5 Interaction Induces Synaptogenesis during Early Hippocampal Development

Cited by 64 publications

References 72 publications

Connexin 43 stabilizes astrocytes in a stroke-like milieu to facilitate neuronal recovery

Connexin 43 stabilizes astrocytes in a stroke-like milieu to facilitate neuronal recovery

Eph receptors and ephrins in neuron–astrocyte communication at synapses

Activation of EphA Receptors Mediates the Recruitment of the Adaptor Protein Slap, Contributing to the Downregulation ofN-Methyl-d-Aspartate Receptors

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