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Activation of EphA receptors mediates the recruitment of the adaptor protein Slap, contributing to the downregulation of N-methyl-D-aspartate receptors.
Semerdjieva S
,
Abdul-Razak HH
,
Salim SS
,
Yáñez-Muñoz RJ
,
Chen PE
,
Tarabykin V
,
Alifragis P
.
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Regulation 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.
Akaneya,
Ephrin-A5 and EphA5 interaction induces synaptogenesis during early hippocampal development.
2010, Pubmed
Akaneya,
Ephrin-A5 and EphA5 interaction induces synaptogenesis during early hippocampal development.
2010,
Pubmed
Alifragis,
Restricted expression of Slap-1 in the rodent cerebral cortex.
2003,
Pubmed
Arunachalam,
Grammatical form and semantic context in verb learning.
2011,
Pubmed
Bolte,
A guided tour into subcellular colocalization analysis in light microscopy.
2006,
Pubmed
Calò,
Interaction between ephrins/Eph receptors and excitatory amino acid receptors: possible relevance in the regulation of synaptic plasticity and in the pathophysiology of neuronal degeneration.
2006,
Pubmed
Carmona,
Glial ephrin-A3 regulates hippocampal dendritic spine morphology and glutamate transport.
2009,
Pubmed
Cesca,
The synapsins: key actors of synapse function and plasticity.
2010,
Pubmed
Chen,
NS21: re-defined and modified supplement B27 for neuronal cultures.
2008,
Pubmed
Chen,
Protein tyrosine kinase-mediated potentiation of currents from cloned NMDA receptors.
1996,
Pubmed
,
Xenbase
Chen,
Modulation of glycine potency in rat recombinant NMDA receptors containing chimeric NR2A/2D subunits expressed in Xenopus laevis oocytes.
2008,
Pubmed
,
Xenbase
Contractor,
Trans-synaptic Eph receptor-ephrin signaling in hippocampal mossy fiber LTP.
2002,
Pubmed
Cowan,
Vav family GEFs link activated Ephs to endocytosis and axon guidance.
2005,
Pubmed
Dalva,
EphB receptors interact with NMDA receptors and regulate excitatory synapse formation.
2000,
Pubmed
Davis,
Ligands for EPH-related receptor tyrosine kinases that require membrane attachment or clustering for activity.
1994,
Pubmed
Davy,
Compartmentalized signaling by GPI-anchored ephrin-A5 requires the Fyn tyrosine kinase to regulate cellular adhesion.
1999,
Pubmed
Dickson,
Molecular mechanisms of axon guidance.
2002,
Pubmed
Dragone,
SLAP, a regulator of immunoreceptor ubiquitination, signaling, and trafficking.
2009,
Pubmed
Dragone,
Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner.
2006,
Pubmed
Ehlers,
Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system.
2003,
Pubmed
Erreger,
Subunit-specific agonist activity at NR2A-, NR2B-, NR2C-, and NR2D-containing N-methyl-D-aspartate glutamate receptors.
2007,
Pubmed
,
Xenbase
Flanagan,
The ephrins and Eph receptors in neural development.
1998,
Pubmed
Fu,
Cyclin-dependent kinase 5 links extracellular cues to actin cytoskeleton during dendritic spine development.
2007,
Pubmed
Fu,
APC(Cdh1) mediates EphA4-dependent downregulation of AMPA receptors in homeostatic plasticity.
2011,
Pubmed
Fu,
Axonal/glial upregulation of EphB/ephrin-B signaling in mouse experimental ocular hypertension.
2010,
Pubmed
Gao,
Regulation of hippocampal synaptic plasticity by the tyrosine kinase receptor, REK7/EphA5, and its ligand, AL-1/Ephrin-A5.
1998,
Pubmed
Gerlai,
Eph receptors and neural plasticity.
2001,
Pubmed
Gerlai,
Regulation of learning by EphA receptors: a protein targeting study.
1999,
Pubmed
Grant,
Opposing contributions of NR1 and NR2 to protein kinase C modulation of NMDA receptors.
1998,
Pubmed
Grunwald,
Hippocampal plasticity requires postsynaptic ephrinBs.
2004,
Pubmed
Hajós,
An improved method for the preparation of synaptosomal fractions in high purity.
1975,
Pubmed
Henderson,
The receptor tyrosine kinase EphB2 regulates NMDA-dependent synaptic function.
2001,
Pubmed
Henkemeyer,
Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus.
2003,
Pubmed
Irie,
EPHB receptor signaling in dendritic spine development.
2004,
Pubmed
Kalo,
Signal transfer by eph receptors.
1999,
Pubmed
Kato,
Activity-dependent NMDA receptor degradation mediated by retrotranslocation and ubiquitination.
2005,
Pubmed
Kayser,
EphB receptors couple dendritic filopodia motility to synapse formation.
2008,
Pubmed
Kim,
Src-like adaptor protein regulates osteoclast generation and survival.
2010,
Pubmed
Klein,
Eph/ephrin signaling in morphogenesis, neural development and plasticity.
2004,
Pubmed
Knöll,
Ephrin-As as receptors in topographic projections.
2002,
Pubmed
Lau,
Glutamate receptors, neurotoxicity and neurodegeneration.
2010,
Pubmed
Manes,
Slap negatively regulates Src mitogenic function but does not revert Src-induced cell morphology changes.
2000,
Pubmed
Martínez,
Functions of ephrin/Eph interactions in the development of the nervous system: emphasis on the hippocampal system.
2005,
Pubmed
Meima,
AL-1-induced growth cone collapse of rat cortical neurons is correlated with REK7 expression and rearrangement of the actin cytoskeleton.
1997,
Pubmed
Mulvey,
Wavelength-dependent backscattering measurements for quantitative monitoring of apoptosis, part 1: early and late spectral changes are indicative of the presence of apoptosis in cell cultures.
2011,
Pubmed
Murai,
Eph receptors, ephrins, and synaptic function.
2004,
Pubmed
Murai,
Control of hippocampal dendritic spine morphology through ephrin-A3/EphA4 signaling.
2003,
Pubmed
Myers,
Src-like adaptor protein down-regulates T cell receptor (TCR)-CD3 expression by targeting TCRzeta for degradation.
2005,
Pubmed
O'Brien,
The development of excitatory synapses in cultured spinal neurons.
1997,
Pubmed
Pandey,
Characterization of a novel Src-like adapter protein that associates with the Eck receptor tyrosine kinase.
1995,
Pubmed
Papa,
Morphological analysis of dendritic spine development in primary cultures of hippocampal neurons.
1995,
Pubmed
Pasquale,
The Eph family of receptors.
1997,
Pubmed
Pasquale,
Eph-ephrin promiscuity is now crystal clear.
2004,
Pubmed
Pasquale,
Eph receptor signalling casts a wide net on cell behaviour.
2005,
Pubmed
Raymond,
Glutamate receptor modulation by protein phosphorylation.
1994,
Pubmed
Raymond,
Glutamate receptor ion channel properties predict vulnerability to cytotoxicity in a transfected nonneuronal cell line.
1996,
Pubmed
Sosinowski,
Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling.
2000,
Pubmed
Takasu,
Modulation of NMDA receptor-dependent calcium influx and gene expression through EphB receptors.
2002,
Pubmed
Wagey,
Modulation of NMDA-mediated excitotoxicity by protein kinase C.
2001,
Pubmed
Walker-Daniels,
c-Cbl-dependent EphA2 protein degradation is induced by ligand binding.
2002,
Pubmed
Wang,
Negative regulation of EphA2 receptor by Cbl.
2002,
Pubmed
Wang,
Regulation of NMDA receptors by tyrosine kinases and phosphatases.
1994,
Pubmed
Wanisch,
Integration-deficient lentiviral vectors: a slow coming of age.
2009,
Pubmed
Watt,
Activity coregulates quantal AMPA and NMDA currents at neocortical synapses.
2000,
Pubmed
Waxman,
Pharmacokinetics of concurrently administered intravenous lidocaine and flunixin in healthy horses.
2012,
Pubmed
Yun,
EphA family gene expression in the developing mouse neocortex: regional patterns reveal intrinsic programs and extrinsic influence.
2003,
Pubmed
Yáñez-Muñoz,
Effective gene therapy with nonintegrating lentiviral vectors.
2006,
Pubmed
Zheng,
Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition.
1998,
Pubmed
