ucn-1028-c and 6-methyl-2-(phenylethynyl)pyridine

Regulation of surface insertion and internalization of AMPA and NMDA receptors has emerged as a key mechanism for the control of synaptic strength. Regulatory elements for synaptic kainate receptors (KARs) are, however, largely undetermined. We have found that SNAP25 is critical for the synaptic removal of KARs, acting via GluK5 (i.e., KA2) subunits. SNAP25 coimmunoprecipitates with protein complexes containing PICK1, GRIP1, and GluK5 and colocalizes with GluK5 in both hippocampal neurons and transfected HEK293 cells. In hippocampal slices, purified SNAP25 antibodies and blocking peptides caused a GluK5-dependent run-up of KARs-mediated EPSC (EPSC(KAR)) recorded from CA3 pyramidal neurons when included in the patch pipette and prevented activity-dependent long-term depression of EPSC(KAR). As EPSC(KAR) LTD, SNAP25/PICK1/GluK5 interactions are dynamically regulated by PKC.

Topics: Adaptor Proteins, Signal Transducing; Animals; Animals, Newborn; Calcium; Carrier Proteins; Cell Cycle Proteins; Cell Line, Transformed; Cell Line, Tumor; Electric Stimulation; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Hippocampus; Humans; Immunoprecipitation; Luminescent Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Naphthalenes; Nerve Tissue Proteins; Neural Pathways; Neuroblastoma; Neuronal Plasticity; Neurons; Neurotoxins; Nuclear Proteins; Patch-Clamp Techniques; Protein Transport; Pyridines; Rats; Receptors, Kainic Acid; Synapses; Synaptosomal-Associated Protein 25; Transfection; Vesicle-Associated Membrane Protein 2