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The Journal of Neuroscience, May 1, 2002, 22(9):3493-3503
Differential Palmitoylation Directs the AMPA Receptor-Binding Protein ABP to Spines or to Intracellular Clusters
Sunita DeSouza, Jie Fu, Bradley A. States, and Edward B. Ziff Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, New York 10016
Long-term changes in excitatory synapse strength are thought to reflect changes in synaptic abundance of AMPA receptors mediated by receptor trafficking. AMPA receptor-binding protein (ABP) and glutamate receptor-interacting protein (GRIP) are two similar PDZ (postsynaptic density 95/Discs large/zona occludens 1) proteins that interact with glutamate receptors 2 and 3 (GluR2 and GluR3) subunits. Both proteins have proposed roles during long-term potentiation and long-term depression in the delivery and anchorage of AMPA receptors at synapses. Here we report a variant of ABP-L (seven PDZ form of ABP) called pABP-L that is palmitoylated at a cysteine residue at position 11 within a novel 18 amino acid N-terminal leader sequence encoded through differential splicing. In cultured hippocampal neurons, nonpalmitoylated ABP-L localizes with internal GluR2 pools expressed from a Sindbis virus vector, whereas pABP-L is membrane targeted and associates with surface-localized GluR2 receptors at the plasma membrane in spines. Mutation of Cys-11 to alanine blocks the palmitoylation of pABP-L and targets the protein to intracellular clusters, confirming that targeting the protein to spines is dependent on palmitoylation. Non-palmitoylated GRIP is primarily intracellular, but a chimera with the pABP-L N-terminal palmitoylation sequence linked to the body of the GRIP protein is targeted to spines. We suggest that pABP-L and ABP-L provide, respectively, synaptic and intracellular sites for the anchorage of AMPA receptors during receptor trafficking to and from the synapse.
Key words: palmitoylation; glutamate receptor; AMPA receptor; AMPA receptor-binding protein; glutamate receptor interacting protein; alternative splicing
Copyright © 2002 Society for Neuroscience 0270-6474/02/2293493-11$05.00/0
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