SAP97 IS ASSOCIATED WITH THE LPHA-AMINO-3-HYDROXY-5-METHYLISOXAZOLE-4-PROPIONIC ACID RECEPTOR GLUR1 SUBUNIT

Rapid glutamatergic synaptic transmission is mediated by ionotropic gl utamate receptors and depends on their precise localization at postsyn aptic membranes opposing the presynaptic neurotransmitter release site s. Postsynaptic localization of N-methyl-D-aspartate-type glutamate re ceptors may be mediated by the synapse-associated proteins (SAPs) SAP9 0, SAP102, and chapsyn-110, SAPs contain three PDZ domains that can in teract with the C termini of proteins such as N-methyl-D-aspartate rec eptor 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 lpha-amino-3-hydroxy-5-methylisoxazole-4-p ropionic acid (AMPA)-type glutamate receptors, AMPA receptors are prob ably 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 rece ptor complexes immunoprecipitated from detergent extracts of rat brain . After treatment of rat brain membrane fractions with the cross-linke r dithiobis(succinimidylpropionate) and solubilization with sodium dod ecylsulfate, SAP97 was associated with GluR1 but not GluR2 or GluR3. I n vitro experiments with recombinant proteins indicate that SAP97 spec ifically associates with the C terminus of GluR1 but not other AMPA re ceptor subunits, Our findings suggest that SAP97 may be involved in lo calizing AMPA receptors at postsynaptic sites through its interaction with the GluR1 subunit.