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dc.contributor.authorColeman, Sarah K.
dc.contributor.authorCai, Chunlin
dc.contributor.authorKalkkinen, Nisse
dc.contributor.authorKorpi, Esa R.
dc.contributor.authorKeinanen, Kari
dc.contributor.editorMei, Lin
dc.date.accessioned2012-10-26T16:26:46Z
dc.date.available2012-10-26T16:26:46Z
dc.date.issued2010-01-14en_US
dc.identifier.citationPLoS One. 2010 Jan 14; 5(1):e8715en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid20090852en_US
dc.identifier.doi10.1371/journal.pone.0008715en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/576
dc.description.abstractBackground: Specific delivery to synapses of a-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors with long-tailed subunits is believed to be a key event in many forms of activity-dependent changes in synaptic strength. GluA1, the best characterized long-tailed AMPA receptor subunit, contains a C-terminal class I PDZ binding motif, which mediates its interaction with scaffold and trafficking proteins, including synapse-associated protein 97 (SAP97). In GluA4, another long-tailed subunit implicated in synaptic plasticity, the PDZ motif is blocked by a single proline residue. This feature is highly conserved in vertebrates, whereas the closest invertebrate homologs of GluA4 have a canonical class I PDZ binding motif. In this work, we have examined the role of GluA4 in PDZ interactions
dc.description.abstractMethodology/Principal Findings: Deletion of the carboxy-terminal proline residue of recombinant GluA4 conferred avid binding to SAP97 in cultured cells as shown by coimmunoprecipitation, whereas wild-type GluA4 did not associate with SAP97. Native GluA4 and SAP97 coimmunoprecipitated from mouse brain independently of the GluA1 subunit, supporting the possibility of in vivo PDZ interaction. To obtain evidence for or against the exposure of the PDZ motif by carboxyterminal processing of native GluA4 receptors, we generated an antibody reagent specific for proline-deleted GluA4 C-terminus. Immunoprecipitation and mass spectrometric analyses indicated that the carboxyl-terminus of native GluA4 AMPA receptors is intact and that the postulated single-residue cleavage does not occur to any significant extent.
dc.description.abstractConclusion/Significance: We conclude that native GluA4 receptors are not capable of canonical PDZ interactions and that their association with SAP97 is likely to be indirect.
dc.rightsColeman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiochemistry/Biomacromolecule-Ligand Interactionsen_US
dc.subjectBiochemistry/Cell Signaling and Trafficking Structuresen_US
dc.subjectBiotechnology/Protein Chemistry and Proteomicsen_US
dc.subjectCell Biology/Neuronal Signaling Mechanismsen_US
dc.subjectNeuroscience/Neuronal Signaling Mechanismsen_US
dc.titleAnalysis of the Potential Role of GluA4 Carboxyl-Terminus in PDZ Interactionsen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2806832en_US
dc.contributor.corporatenameDepartment of Neurology
dc.contributor.corporatenameCollege of Graduate Studies
refterms.dateFOA2019-04-09T21:13:14Z
html.description.abstractBackground: Specific delivery to synapses of a-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors with long-tailed subunits is believed to be a key event in many forms of activity-dependent changes in synaptic strength. GluA1, the best characterized long-tailed AMPA receptor subunit, contains a C-terminal class I PDZ binding motif, which mediates its interaction with scaffold and trafficking proteins, including synapse-associated protein 97 (SAP97). In GluA4, another long-tailed subunit implicated in synaptic plasticity, the PDZ motif is blocked by a single proline residue. This feature is highly conserved in vertebrates, whereas the closest invertebrate homologs of GluA4 have a canonical class I PDZ binding motif. In this work, we have examined the role of GluA4 in PDZ interactions
html.description.abstractMethodology/Principal Findings: Deletion of the carboxy-terminal proline residue of recombinant GluA4 conferred avid binding to SAP97 in cultured cells as shown by coimmunoprecipitation, whereas wild-type GluA4 did not associate with SAP97. Native GluA4 and SAP97 coimmunoprecipitated from mouse brain independently of the GluA1 subunit, supporting the possibility of in vivo PDZ interaction. To obtain evidence for or against the exposure of the PDZ motif by carboxyterminal processing of native GluA4 receptors, we generated an antibody reagent specific for proline-deleted GluA4 C-terminus. Immunoprecipitation and mass spectrometric analyses indicated that the carboxyl-terminus of native GluA4 AMPA receptors is intact and that the postulated single-residue cleavage does not occur to any significant extent.
html.description.abstractConclusion/Significance: We conclude that native GluA4 receptors are not capable of canonical PDZ interactions and that their association with SAP97 is likely to be indirect.


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