The Junction-associated Protein AF-6 Interacts and Clusters with Specific Eph Receptor Tyrosine Kinases at Specialized Sites of Cell–Cell Contact in the Brain

Büchert, Michael; Schneider, Stefan; Meskenaïte, Virginia; Adams, Mark; Canaani, Eli; Baechi, Thomas; Moelling, Karin; Hovens, Christopher M.

doi:10.1083/jcb.144.2.361

Cited by 180 publications

(133 citation statements)

References 43 publications

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…We were interested in identifying novel signaling interactions that may be important in the regulation of neuronal morphology downstream of EphA4. A potential site of interaction that has not been well characterized for EphA4 is its C-terminal PDZ-binding motif (Torres et al, 1998;Buchert et al, 1999). To identify PDZ domain proteins that may interact with EphA4, we performed GST pull-down assays using the PDZ domains of several candidate proteins known to be expressed in neurons.…”

Section: Resultsmentioning

confidence: 99%

“…Although other EphA receptors have been reported to associate with PDZ domain-containing proteins, the functional significance of these interactions is not yet known (Torres et al, 1998;Buchert et al, 1999). Associations mediated by the PDZ domain-binding motifs of EphB receptors (the other class of Eph receptors) have been shown to regulate Eph receptor trafficking and clustering in dendrites, dendrite morphogenesis, and glutamatergic synaptogenesis (Torres et al, 1998;Hoogenraad et al, 2005;Kayser et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The EphA4 Receptor Regulates Neuronal Morphology through SPAR-Mediated Inactivation of Rap GTPases

Richter

Murai²,

Bourgin³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The EphA4 Receptor Regulates Neuronal Morphology through SPAR-Mediated Inactivation of Rap GTPases

Richter

Murai²,

Bourgin³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

“…The kinase activity of EphB is involved in the formation of NMDA receptor-containing postsynaptic specializations, although it is not required for the initial interaction of EphB and NMDA receptors. The localization of ephrinB and EphB was not examined in the latter study, although it has been shown that during early development, EphB is present on axons and ephrinB is localized on target cells (37), and that EphB is localized on the postsynaptic cell in the adult hippocampus (38). It is possible that EphB͞NMDA receptor complex forms at postsynaptic sites, and a signal is transmitted to the nascent presynaptic site through ephrinB, because the ephrinB͞EphB complex is capable of reciprocal signaling (39).…”

Section: Retrograde Signaling During Synaptogenesismentioning

confidence: 99%

Retrograde signaling at central synapses

Tao

Poo

2001

Proc. Natl. Acad. Sci. U.S.A.

124

View full text Add to dashboard Cite

Transcellular retrograde signaling from the postsynaptic target cell to the presynaptic neuron plays critical roles in the formation, maturation, and plasticity of synaptic connections. We here review recent progress in our understanding of the retrograde signaling at developing central synapses. Three forms of potential retrograde signals-membrane-permeant factors, membrane-bound factors, and secreted factors-have been implicated at both developing and mature synapses. Although many of these signals may be active constitutively, retrograde factors produced in association with activity-dependent synaptic plasticity, e.g., long-term potentiation and long-term depression, are of particular interest, because they may induce modification of neuronal excitability and synaptic transmission, functions directly related to the processing and storage of information in the nervous system. N eural information coded by the action potential is transmitted through a chemical synapse in the anterograde direction by release of neurotransmitters, neuropeptides, and other protein factors from the presynaptic terminal. These molecules produce immediate changes in the membrane potential as well as long-term structural and metabolic changes in the postsynaptic cell. Over the past several decades, it has become increasingly clear that information exchange at the synapse is bidirectional: the postsynaptic cell also provides a variety of retrograde signals to the presynaptic neuron. This reciprocal interaction is crucial for the differentiation and maintenance of the presynaptic cell as well as the formation and maturation of the synapse. The general notion of retrograde signaling involves postsynaptic production of a signal, either constitutively or triggered by synaptic activity, that acts on the presynaptic neuron through the following mechanisms. First, the retrograde signal can be carried by a membrane-permeant molecule that diffuses across the plasma membranes from the postsynaptic cell directly into the presynaptic nerve terminal. Second, membraneimpermeant but soluble factors can be packaged and secreted via exocytotic vesicles by the postsynaptic cell and exert the retrograde action by binding and activation of receptors on the presynaptic membrane. Third, direct signaling through the synaptic cleft may be accomplished through mediation of physically coupled pre-and postsynaptic membrane-bound proteins, including transmembrane proteins as well as those secreted and immobilized in the extracellular matrix within the synaptic cleft. This review will summarize recent progress in the study of retrograde regulation at central synapses, with a focus on the role of retrograde interaction in the formation and activitydependent plasticity of synapses. Some aspects of this subject have been more extensively reviewed elsewhere (1). An excellent review of signaling at developing neuromuscular junctions (NMJs) has also appeared recently (2). Retrograde Signaling During SynaptogenesisOur present understanding of the process of synaptogenesis...

show abstract

“…Both subclasses of ephrin are membrane-attached: ephrin-As are bound by glycosylphosphatidylinositol (GPI) linkage and ephrin-Bs are transmembraneous. We focus here on the role of EphB-ephrin-B interactions in synaptogenesis because the preponderance of data implicates these subtypes, although signalling between neuronal EphAs and glial ephrin-As has also been shown to modify dendritic spine morphogenesis 38 , and EphA7 receptors are found at the postsynaptic density in the hippocampus 39 . Ephrin-B binding to EphBs results in bidirectional signalling between the receptor-and ligand-containing cells, thereby permitting contact-mediated trans-cellular signalling.…”

Section: Ephbs and Ephrin-bsmentioning

confidence: 99%

Cell adhesion molecules: signalling functions at the synapse

2007

View full text Add to dashboard Cite

Many cell adhesion molecules are localized at synaptic sites in neuronal axons and dendrites. These molecules bridge pre-and postsynaptic specializations but do far more than simply provide a mechanical link between cells. In this review, we will discuss the roles these proteins have during development and at mature synapses. Synaptic adhesion proteins participate in the formation, maturation, function and plasticity of synaptic connections. Together with conventional synaptic transmission mechanisms, these molecules are an important element in the trans-cellular communication mediated by synapses.CNS synapses are specialized sites of cell-cell contact that mediate the transmission of information between neurons. Synapses are a key site of regulation within neural networks and are characterized by multi-protein complexes arranged at tightly apposed pre-and postsynaptic terminals. Communication between neurons at synapses is mediated primarily by neurotransmitter release and by the gating of postsynaptic receptor ion channels, but a growing body of evidence indicates that signalling is also mediated by adhesion molecules that interact in a homo-or heterophilic fashion across the synaptic cleft. As at other cell-cell junctions, such as epithelial tight junctions or the immune synapse, research in a variety of neuronal subtypes has shown that synaptically localized cell adhesion molecules (SAMs) are not merely static structural components but are often dynamic regulators of synapse function. When pairs of SAMs interact, they can induce the formation of new synapses or modulate the function of existing synapses through signalling cascades or secondary protein-protein interactions. Numerous studies indicate that interactions between specific SAMs can control synapse formation, regulate dendritic spine morphology, modify synaptic receptor function and modulate synaptic plasticity. So, SAMs can mediate physical interactions between cells and act at multiple steps in the life of a synapse (FIG. 1).Here, we focus on well-studied classes of SAMs that have roles at both developing and mature synapses, namely neurexins and neuroligins, EphBs and ephrin-Bs, immunoglobulinCorrespondence to: M.B.D. dalva@mail.med.upenn.edu. Competing interests statementThe authors declare no competing financial interests. Note added in proofIn a recently published manuscript, Futai et al. 144 demonstrate that trans-synaptic β-neurexin-neuroligin interactions can modulate presynaptic function. The authors show that overexpression or knockdown of PSD-95 in the postsynaptic cell modulates presynaptic release probability, and that these effects are blocked when trans-synaptic β-neurexin-neuroligin signalling is disrupted. This paper provides further evidence that SAMs act to regulate synaptic function. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript (Ig)-containing cell adhesion molecules and cadherins. We discuss the ways in which these proteins seem to control discrete aspects of synaptic develop...

show abstract

The Junction-associated Protein AF-6 Interacts and Clusters with Specific Eph Receptor Tyrosine Kinases at Specialized Sites of Cell–Cell Contact in the Brain

Cited by 180 publications

References 43 publications

The EphA4 Receptor Regulates Neuronal Morphology through SPAR-Mediated Inactivation of Rap GTPases

The EphA4 Receptor Regulates Neuronal Morphology through SPAR-Mediated Inactivation of Rap GTPases

Retrograde signaling at central synapses

Cell adhesion molecules: signalling functions at the synapse

Contact Info

Product

Resources

About