Notch receptor-ligand binding facilitates extracellular vesicle-mediated neuron-to-neuron communication

Yi Zhi Wang, Charlotte C.M. Castillon, Kamil K. Gebis, Elizabeth T. Bartom, Alessandra d'Azzo, Anis Contractor, Jeffrey N. Savas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Extracellular vesicles (EVs) facilitate intercellular communication by transferring cargo between cells in a variety of tissues. However, how EVs achieve cell-type-specific intercellular communication is still largely unknown. We found that Notch1 and Notch2 proteins are expressed on the surface of neuronal EVs that have been generated in response to neuronal excitatory synaptic activity. Notch ligands bind these EVs on the neuronal plasma membrane, trigger their internalization, activate the Notch signaling pathway, and drive the expression of Notch target genes. The generation of these neuronal EVs requires the endosomal sorting complex required for transport-associated protein Alix. Adult Alix conditional knockout mice have reduced hippocampal Notch signaling activation and glutamatergic synaptic protein expression. Thus, EVs facilitate neuron-to-neuron communication via the Notch receptor-ligand system in the brain.

Original languageEnglish (US)
Article number113680
JournalCell reports
Issue number2
StatePublished - Feb 27 2024


  • Alix
  • CP: Neuroscience
  • Notch
  • excitatory synaptic activity
  • extracellular vesicles
  • glutamatergic synapse
  • neuron communication

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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