Analysis of the Potential Role of GluA4 Carboxyl-Terminus in PDZ Interactions
MetadataShow full item record
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
Methodology/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.
Conclusion/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.
CitationPLoS One. 2010 Jan 14; 5(1):e8715
- Selective binding of synapse-associated protein 97 to GluR-A alpha-amino-5-hydroxy-3-methyl-4-isoxazole propionate receptor subunit is determined by a novel sequence motif.
- Authors: Cai C, Coleman SK, Niemi K, Keinänen K
- Issue date: 2002 Aug 30
- Sequential delivery of synaptic GluA1- and GluA4-containing AMPA receptors (AMPARs) by SAP97 anchored protein complexes in classical conditioning.
- Authors: Zheng Z, Keifer J
- Issue date: 2014 Apr 11
- SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit.
- Authors: Leonard AS, Davare MA, Horne MC, Garner CC, Hell JW
- Issue date: 1998 Jul 31
- The carboxyl terminus of the prolactin-releasing peptide receptor interacts with PDZ domain proteins involved in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor clustering.
- Authors: Lin SH, Arai AC, Wang Z, Nothacker HP, Civelli O
- Issue date: 2001 Nov
- Crystal structure of the second PDZ domain of SAP97 in complex with a GluR-A C-terminal peptide.
- Authors: von Ossowski I, Oksanen E, von Ossowski L, Cai C, Sundberg M, Goldman A, Keinänen K
- Issue date: 2006 Nov