Synapse-associated protein 97 selectively associates with a subset of AMPA receptors early in their biosynthetic pathway.
The regulation of AMPA receptors at the postsynaptic membrane is a fundamental component of synaptic plasticity. In the hippocampus, the induction of long-term potentiation increases the delivery of GluR1, a major AMPA receptor subunit in hippocampal pyramidal neurons, to the synaptic plasma membrane through a mechanism that requires the PDZ binding domain of GluR1. Synapse-associated protein 97 (SAP97), a member of the membrane-associated guanylate kinase family, is believed to associate with AMPA receptors (AMPARs) containing the GluR1 subunit, but the functional significance of these interactions is unclear. We investigated the interaction of GluR1 with SAP97, the only PDZ protein known to interact with GluR1. We find that interactions involving SAP97 and GluR1 occur early in the secretory pathway, while the receptors are in the endoplasmic reticulum or cis-Golgi. In contrast, few synaptic receptors associate with SAP97, suggesting that SAP97 dissociates from the receptor complex at the plasma membrane. We also show that internalization of GluR1, as triggered by NMDAR activation, does not require SAP97. These results implicate GluR1-SAP97 interactions in mechanisms underlying AMPA receptor targeting.
Sans
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N
Laboratory of Neurochemistry, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892-8027, USA. sansn@nidcd.nih.gov
Racca
C
C
Petralia
R S
RS
Wang
Y X
YX
McCallum
J
J
Wenthold
R J
RJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019921:Biotinylation; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D008565:Membrane Proteins; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C501119:Dlg1 protein, rat; C104722:glutamate receptor ionotropic, AMPA 2