Synaptic proteome diversity is shaped by the levels of glutamate receptors and their regulatory proteins

Rita Reig-Viader, Diego del Castillo-Berges, Albert Burgas-Pau, Daniel Arco-Alonso, Oriana Zerpa-Rios, David Ramos-Vicente, Javier Picañol, Aida Castellanos, David Soto, Nerea Roher, Carlos Sindreu and Àlex Bayés ()
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Rita Reig-Viader: Institut de Recerca Sant Pau (IR SANT PAU), Molecular Physiology of the Synapse Laboratory
Diego del Castillo-Berges: Institut de Recerca Sant Pau (IR SANT PAU), Molecular Physiology of the Synapse Laboratory
Albert Burgas-Pau: Institut de Recerca Sant Pau (IR SANT PAU), Molecular Physiology of the Synapse Laboratory
Daniel Arco-Alonso: Institut de Recerca Sant Pau (IR SANT PAU), Molecular Physiology of the Synapse Laboratory
Oriana Zerpa-Rios: Institut de Recerca Sant Pau (IR SANT PAU), Molecular Physiology of the Synapse Laboratory
David Ramos-Vicente: Institut de Recerca Sant Pau (IR SANT PAU), Molecular Physiology of the Synapse Laboratory
Javier Picañol: University of Barcelona, Neurophysiology Laboratory, Department of Biomedicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences
Aida Castellanos: University of Barcelona, Neurophysiology Laboratory, Department of Biomedicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences
David Soto: University of Barcelona, Neurophysiology Laboratory, Department of Biomedicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences
Nerea Roher: Bellaterra (Cerdanyola del Vallès), Institute of Biotechnology and Biomedicine (IBB) and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona
Carlos Sindreu: August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
Àlex Bayés: Institut de Recerca Sant Pau (IR SANT PAU), Molecular Physiology of the Synapse Laboratory

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Synapses formed by equivalent pairs of pre- and postsynaptic neurons have similar electrophysiological characteristics, belonging to the same type. However, these are generally confined to microscopic brain regions, precluding their proteomic analysis. This fact has greatly limited our ability to investigate the molecular basis of synaptic physiology. We introduce a procedure to characterise the synaptic proteome of microscopic brain regions and explore the molecular diversity among the synapses forming the trisynaptic circuit in the mouse hippocampus. While we observe a remarkable proteomic diversity among these synapses, we also report that proteins involved in the regulation of the function of glutamate receptors are differentially expressed in all of them. Moreover, neuron-specific gene expression programs would contribute to their regulation. Here, we introduce a combined proteomics and transcriptomics analysis uncovering a previously unrecognized neuron-specific control of synaptic proteome diversity, directed towards the regulation of glutamate receptors and their regulatory proteins.

Date: 2025
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DOI: 10.1038/s41467-025-65490-9

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