Experience-Induced Remodeling of the Hippocampal Post-synaptic Proteome and Phosphoproteome

• DOI: 10.1016/j.mcpro.2023.100661
• Publication Date: 2023-10-07T00:50:12Z
• Authors: Seok Heo; Taewook Kang; Alexei M. Bygrave; Martin R. Larsen; Richard L. Huganir
• Keywords: Proteome

The postsynaptic density (PSD) of excitatory synapses contains a highly organized protein network with thousands proteins and is key node in the regulation synaptic plasticity. To gain new mechanistic insight into experience-induced changes PSD, we examined global dynamics hippocampal PSD proteome phosphoproteome mice following four different types experience. Mice were trained using an inhibitory avoidance (IA) task fractions isolated from individual to investigate molecular mechanisms underlying experience-dependent remodeling synapses. We developed strategy identify quantify relatively low level site-specific phosphorylation hippocampus, by modified iTRAQ-based TiSH protocol. In identified 3938 2761 phosphoproteins sequential covering total 4968 unique groups (at least two peptides including peptide). On phosphoproteins, 6188 unambiguous phosphosites (75%<site-localization probability). Strikingly, significantly IA-regulated large fraction these displayed overall decrease level. Bioinformatic analysis that regulated IA annotated for involvement glutamate receptor functionality, RHO GTPase cycle, also kinases, phosphatases, their respective training or immediate shock. Furthermore, found AMPA surface expression was Mg2+/Mn2+ dependent phosphatase 1H (Ppm1h). Together, results unravel dynamic upon learning shock serve as resource elucidating induced