title: Activity-dependent protein dynamics define interconnected cores of co-regulated postsynaptic proteins.
abstract: Synapses are highly dynamic structures that mediate cell-cell communication in the central nervous system. Their molecular composition is altered in an activity-dependent fashion, which modulates the efficacy of subsequent synaptic transmission events. Whereas activity-dependent trafficking of individual key synaptic proteins into and out of the synapse has been characterized previously, global activity-dependent changes in the synaptic proteome have not been studied. To test the feasibility of carrying out an unbiased large-scale approach, we investigated alterations in the molecular composition of synaptic spines following mass stimulation of the central nervous system induced by pilocarpine. We observed widespread changes in relative synaptic abundances encompassing essentially all proteins, supporting the view that the molecular composition of the postsynaptic density is tightly regulated. In most cases, we observed that members of gene families displayed coordinate regulation even when they were not known to physically interact. Analysis of correlated synaptic localization revealed a tightly co-regulated cluster of proteins, consisting of mainly glutamate receptors and their adaptors. This cluster constitutes a functional core of the postsynaptic machinery, and changes in its size affect synaptic strength and synaptic size. Our data show that the unbiased investigation of activity-dependent signaling of the postsynaptic density proteome can offer valuable new information on synaptic plasticity.
authors.affiliation: Mass Spectrometry Facility, Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94158-2517, USA.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Trinidad
authors.forename: Agnes
authors.initials: A
authors.lastname: Thalhammer
authors.forename: Alma L
authors.initials: AL
authors.lastname: Burlingame
authors.forename: Ralf
authors.initials: R
authors.lastname: Schoepfer
mesh_terms: D000818:Animals; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D010862:Pilocarpine / Q000494:pharmacology; D057907:Post-Synaptic Density / Q000378:metabolism*; D021381:Protein Transport; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D017470:Receptors, Glutamate; D010862:Pilocarpine; D051528:Guanylate Kinases