SAP97 is associated with the α-amino-3-hydroxy-5-methylisoxazole-4- propionic acid receptor GluR1 subunit

A. Soren Leonard, Monika A. Davare, Mary C Horne, Craig C. Garner, Johannes W Hell

Research output: Contribution to journalArticle

336 Citations (Scopus)

Abstract

Rapid glutamatergic synaptic transmission is mediated by ionotropic glutamate receptors and depends on their precise localization at postsynaptic membranes opposing the presynaptic neurotransmitter release sites. Postsynaptic localization of N-methyl-D-aspartate-type glutamate receptors may be mediated by the synapse-associated proteins (SAPs) SAP90, SAP102, and chapsyn-110. SAPs contain three PDZ domains that can interact with the C termini of proteins such as N-methyl-D-aspartate receptor subunits that carry a serine or threonine at the -2 position and a valine, isoleucine, or leucine at the very C terminus (position 0). We now show that SAP97, a SAP whose function at the synapse has been unclear, is associated with α-amino-3- hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors. AMPA receptors are probably tetramers and are formed by two or more of the four AMPA receptor subunits GluR1-4. GluR1 possesses a C-terminal consensus sequence for interactions with PDZ domains of SAPs. SAP97 was present in AMPA receptor complexes immunoprecipitated from detergent extracts of rat brain. After treatment of rat brain membrane fractions with the cross-linker dithiobis(succinimidylpropionate) and solubilization with sodium dodecylsulfate, SAP97 was associated with GluR1 but not GluR2 or GluR3. In vitro experiments with recombinant proteins indicate that SAP97 specifically associates with the C terminus of GluR1 but not other AMPA receptor subunits. Our findings suggest that SAP97 may be involved in localizing AMPA receptors at postsynaptic sites through its interaction with the GluR1 subunit.

Original languageEnglish (US)
Pages (from-to)19518-19524
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number31
DOIs
StatePublished - Jul 31 1998
Externally publishedYes

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Synapses
PDZ Domains
Glutamate Receptors
Proteins
N-Methyl-D-Aspartate Receptors
Rats
Brain
Membranes
Ionotropic Glutamate Receptors
Isoleucine
Consensus Sequence
Valine
N-Methylaspartate
Threonine
Protein C
Recombinant Proteins
Leucine
Synaptic Transmission
Detergents
Serine

ASJC Scopus subject areas

  • Biochemistry

Cite this

SAP97 is associated with the α-amino-3-hydroxy-5-methylisoxazole-4- propionic acid receptor GluR1 subunit. / Leonard, A. Soren; Davare, Monika A.; Horne, Mary C; Garner, Craig C.; Hell, Johannes W.

In: Journal of Biological Chemistry, Vol. 273, No. 31, 31.07.1998, p. 19518-19524.

Research output: Contribution to journalArticle

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