Synaptic proteome diversity is shaped by the levels of glutamate receptors and their regulatory proteins
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.
Authors
- David Ramos-Vicente (ORCID: https://orcid.org/0000-0002-2730-0850)
- Rita Reig‐Viader (ORCID: https://orcid.org/0000-0002-6893-6177)
- Àlex Bayés (ORCID: https://orcid.org/0000-0002-5265-6306)
- Carlos Sindreu (ORCID: https://orcid.org/0000-0001-6730-8278)
- Nerea Roher (ORCID: https://orcid.org/0000-0002-6659-4038)
- Aida Castellanos (ORCID: https://orcid.org/0000-0003-0405-8480)
- Daniel Arco-Alonso
- Javier Picañol (ORCID: https://orcid.org/0000-0002-1270-7105)
- David Soto (ORCID: https://orcid.org/0000-0001-7995-3805)
- Diego del Castillo-Berges
- Albert Burgas-Pau (ORCID: https://orcid.org/0009-0006-8828-7430)
- Oriana Zerpa-Rios (ORCID: https://orcid.org/0000-0002-4405-3812)
Institutions
- Universitat Autònoma de Barcelona (ES)
- Instituto de Salud Carlos III (ES)
- Hospital de Sant Pau (ES)
- Centre de Recerca en Sanitat Animal (ES)
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-25
- DOI
- https://doi.org/10.1038/s41467-025-65490-9
- Citations
- 1
- Primary Topic
- Neuroscience and Neuropharmacology Research
- Type
- article
- Field-Weighted Citation Impact
- 0.91
Funders
- Centres de Recerca de Catalunya
- Generalitat de Catalunya
- Universitat Autònoma de Barcelona
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación