title: Differential association of postsynaptic signaling protein complexes in striatum and hippocampus.
abstract: Distinct physiological stimuli are required for bidirectional synaptic plasticity in striatum and hippocampus, but differences in the underlying signaling mechanisms are poorly understood. We have begun to compare levels and interactions of key excitatory synaptic proteins in whole extracts and subcellular fractions isolated from micro-dissected striatum and hippocampus. Levels of multiple glutamate receptor subunits, calcium/calmodulin-dependent protein kinase II (CaMKII), a highly abundant serine/threonine kinase, and spinophilin, a F-actin and protein phosphatase 1 (PP1) binding protein, were significantly lower in striatal extracts, as well as in synaptic and/or extrasynaptic fractions, compared with similar hippocampal extracts/fractions. However, CaMKII interactions with spinophilin were more robust in striatum compared with hippocampus, and this enhanced association was restricted to the extrasynaptic fraction. NMDAR GluN2B subunits associate with both spinophilin and CaMKII, but spinophilin-GluN2B complexes were enriched in extrasynaptic fractions whereas CaMKII-GluN2B complexes were enriched in synaptic fractions. Notably, the association of GluN2B with both CaMKII and spinophilin was more robust in striatal extrasynaptic fractions compared with hippocampal extrasynaptic fractions. Selective differences in the assembly of synaptic and extrasynaptic signaling complexes may contribute to differential physiological regulation of excitatory transmission in striatum and hippocampus.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt Kennedy Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. anthony.baucum@vanderbilt.edu
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Baucum
authors.forename: Abigail M
authors.initials: AM
authors.lastname: Brown
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Colbran
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism; D000099273:Neurabins
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D008840:Microfilament Proteins; D009218:Myosins; D009419:Nerve Tissue Proteins; D054645:Protein Phosphatase 1; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D033921:Vesicular Transport Proteins; D000099273:Neurabins; C121001:NR2B NMDA receptor; C033652:postsynaptic density proteins