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Conference Paper: Regulation of AMPA-type glutamate receptor trafficking by proheparanase in synaptic plasticity

TitleRegulation of AMPA-type glutamate receptor trafficking by proheparanase in synaptic plasticity
Authors
Issue Date2011
PublisherSociety for Neuroscience.
Citation
The 2011 Annual Meeting of the Society for Neuroscience, Washington, D.C., 12-16 November 2011. In Abstract Book of Neuroscience, 2011, p. 244-245 How to Cite?
AbstractSynaptic plasticity is the activity-dependent modification of the strength of synaptic transmission. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) at excitatory synapse mediate fast neurotransmission. Membrane depolarization of postsynaptic neurons then triggers Ca2+ influx that upregulates membrane insertion of AMPARs, resulting in long-lasting potentiation of excitatory post-synaptic potential. Perineuronal heparan sulfates (HS) are implicated in controlling the open-state of AMPARs for the maintenance of synaptic strength. Treatment of hippocampal slice cultures with heparitinase, a bacterial HS-cleaving enzyme, decreases hippocampal LTP on a dose-dependent manner. Our finding of neuronal expression of heparanase, a mammalian HS-cleaving enzyme, led us to test if (1) neuronal heparanase is secreted as the pro-form or the active form and (2) if binding of the secreted form to perineuronal HS plays a role in synaptic plasticity. Hippocampal neurons in culture were treated with phorbol ester to stimulate secretion from vesicular stores. Western blot analysis of secreted material revealed the pro-form. Synaptosome preparations also indicated enrichment in proheparanse. Synaptosome preparations subjected to co-immunoprecipitation studies revealed AMPAR subunits (GluA1 and GluA2/3) binding to both syndecan-3 (a transmembrane HS proteoglycan of neurons) and proheparanase, suggesting their clustering in a functional complex. Treatment of hippocampal neuron cultures with recombinant proheparanase triggered internalization of proheparanase together with perineuronal HS-proteoglycans and AMPARs. Treatment of hippocampal slices with recombinant proheparanase resulted in declines in both basal synaptic strength and LTP. Taken together, the results indicate neuronal secretion of proheparanase as a novel mechanism that contributes to synaptic plasticity by re-setting AMPAR level at the synapse.
DescriptionPoster Session 870 - Synaptic Plasticity: Homeostatic II - Theme B: Neural Excitability, Synapses, and Glia: Cellular Mechanisms: no. 870.09/D41
Persistent Identifierhttp://hdl.handle.net/10722/146975

 

DC FieldValueLanguage
dc.contributor.authorLam, YLen_US
dc.contributor.authorCham, WCen_US
dc.contributor.authorMa, CWen_US
dc.contributor.authorChan, YSen_US
dc.contributor.authorShum, DKYen_US
dc.date.accessioned2012-05-23T05:51:33Z-
dc.date.available2012-05-23T05:51:33Z-
dc.date.issued2011en_US
dc.identifier.citationThe 2011 Annual Meeting of the Society for Neuroscience, Washington, D.C., 12-16 November 2011. In Abstract Book of Neuroscience, 2011, p. 244-245en_US
dc.identifier.urihttp://hdl.handle.net/10722/146975-
dc.descriptionPoster Session 870 - Synaptic Plasticity: Homeostatic II - Theme B: Neural Excitability, Synapses, and Glia: Cellular Mechanisms: no. 870.09/D41-
dc.description.abstractSynaptic plasticity is the activity-dependent modification of the strength of synaptic transmission. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) at excitatory synapse mediate fast neurotransmission. Membrane depolarization of postsynaptic neurons then triggers Ca2+ influx that upregulates membrane insertion of AMPARs, resulting in long-lasting potentiation of excitatory post-synaptic potential. Perineuronal heparan sulfates (HS) are implicated in controlling the open-state of AMPARs for the maintenance of synaptic strength. Treatment of hippocampal slice cultures with heparitinase, a bacterial HS-cleaving enzyme, decreases hippocampal LTP on a dose-dependent manner. Our finding of neuronal expression of heparanase, a mammalian HS-cleaving enzyme, led us to test if (1) neuronal heparanase is secreted as the pro-form or the active form and (2) if binding of the secreted form to perineuronal HS plays a role in synaptic plasticity. Hippocampal neurons in culture were treated with phorbol ester to stimulate secretion from vesicular stores. Western blot analysis of secreted material revealed the pro-form. Synaptosome preparations also indicated enrichment in proheparanse. Synaptosome preparations subjected to co-immunoprecipitation studies revealed AMPAR subunits (GluA1 and GluA2/3) binding to both syndecan-3 (a transmembrane HS proteoglycan of neurons) and proheparanase, suggesting their clustering in a functional complex. Treatment of hippocampal neuron cultures with recombinant proheparanase triggered internalization of proheparanase together with perineuronal HS-proteoglycans and AMPARs. Treatment of hippocampal slices with recombinant proheparanase resulted in declines in both basal synaptic strength and LTP. Taken together, the results indicate neuronal secretion of proheparanase as a novel mechanism that contributes to synaptic plasticity by re-setting AMPAR level at the synapse.-
dc.languageengen_US
dc.publisherSociety for Neuroscience.-
dc.relation.ispartofAbstracts of Neuroscienceen_US
dc.rightsAbstract Book of Neuroscience. Copyright © Society for Neuroscience.-
dc.titleRegulation of AMPA-type glutamate receptor trafficking by proheparanase in synaptic plasticityen_US
dc.typeConference_Paperen_US
dc.identifier.emailCham, WC: felixcwc@hku.hken_US
dc.identifier.emailMa, CW: cwma2010@hku.hken_US
dc.identifier.emailChan, YS: yschan@hku.hken_US
dc.identifier.emailShum, DKY: shumdkhk@hkucc.hku.hk-
dc.identifier.authorityChan, YS=rp00318en_US
dc.identifier.authorityShum, DKY=rp00321en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros199608en_US
dc.identifier.spage244-
dc.identifier.epage245-
dc.publisher.placeUnited States-
dc.description.otherThe 2011 Annual Meeting of the Society for Neuroscience, Washington, D.C., 12-16 November 2011. In Abstract Book of Neuroscience, 2011, p. 244-245-

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