Synaptic protein interaction networks encode experience by assuming stimulus-specific and brain-region-specific states

Abstract

Highlights d Synaptic protein interaction networks differentiate NMDA versus DHPG stimulation d NMDA stimulation produces network responses that differ by brain region d Eyeblink conditioning induces region-and paradigm-specific network changes d Proteomic composition and sensory input determine protein network response

Activity dependent dissociation of the Homer1 interactome

“…Nevertheless, a complex containing Shank-PSD95-NMDAR is well established 8 , 9 . The dissociation of Shanks from Homer1 would be a concise explanation for the coordinated dissociation of Homer1, Shank3, NMDARs, DLGs and SynGAP observed here, and in our previous studies 20 – 22 .…”

“…We performed co-IP followed by quantitative mass spectrometry to characterize the full complement of activity dependent Homer1 interactions in mouse cortex. We cut acute brain slices from 4 WT and 5 Homer1 knockout (KO) mice using the protective recovery method 26 to maintain the slices alive ex vivo, and stimulated them for 5 min with either control artificial cerebro-spinal fluid (aCSF) or 50 mM KCl, which induces depolarization of neurons, calcium-mediated activation of signaling pathways, and dissociation of Homer1 from mGlu5 20 , 22 . We solubilized cortices in 1% NP-40 detergent 27 and immunoprecipitated Homer1 with the mouse monoclonal antibody clone AT1F3, raised against full-length human Homer1 (Fig.…”

“…Our group previously used an antibody-based Quantitative Multiplex co-Immunoprecipitation (QMI) approach to measure activity-dependent changes in synaptic protein–protein interaction networks 20 – 22 . We simultaneously measured ~ 400 binary co-associations among a network of 20 synaptic proteins following treatment of cells or acute brain slices with NMDA, glutamate or KCl.…”

Differential protein-protein interactions underlie signaling mediated by the TCR and a 4-1BB domain–containing CAR

“…Weighted correlation network analysis ( 43 ) (CNA) of interaction intensity matrices identifies “modules” of protein complexes that change in unison across multiple samples and experiments. Previous work demonstrated that interaction modules correlate with experimental stimuli more robustly than do individual interactions because groups of interactions changing in unison are less stochastic than any single interaction ( 44 , 45 ). CNA identified a TCR Stimulation module whose behavior correlated with CD3 stimulation [correlation coefficient (CC) = 0.92] and also correlated to a lesser degree with CD3 and CD19 stimulation (CC = 0.74) (Fig.…”

Protein interaction network analysis of mTOR signaling reveals modular organization

“…An alternative conceptual framework for modeling signal transduction relies on protein interaction networks, whose network topography is acutely post translationally modified during signaling events. In response to environmental stimuli, coordinated groups of protein-protein interactions change their coassociations in unison, modifying the structure and function of the cellular interactome ( 13 , 14 , 15 , 16 , 17 ). The dynamic composition of these protein complexes ( 18 ), and the magnitude of their activation ( 19 ), is thought to instruct specific cellular responses.…”