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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月25日

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  • 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,
  • Àlex Bayés

摘要

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.