Intercellular signaling by ectodomain shedding at the synapse

M. Dolores Martín-de-Saavedra, Marc Dos Santos, Peter Penzes*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations


Ectodomain shedding (ES) is a post-translational protein modification process that plays key roles in health and disease. Many neuronal and synaptic membrane proteins are known to undergo ES, but the complexity of functions regulated by the shed peptides is only beginning to be unraveled. Here, we provide an overview of emerging evidence demonstrating that synaptic ES can mediate autocrine and paracrine signaling. We also discuss how advances in large-scale proteomic analyses are leading to the identification of novel synaptic proteins undergoing ES, as well as the targets and functions of their soluble ectodomains. Finally, we provide an overview of how cerebrospinal fluid (CSF) analyses of shed proteins could be used as a potential source of new biomarkers for neuropsychiatric disorders.

Original languageEnglish (US)
Pages (from-to)483-498
Number of pages16
JournalTrends in Neurosciences
Issue number6
StatePublished - Jun 2022


  • autism
  • neurodegeneration
  • plasticity
  • proteomics
  • sheddome
  • synapse

ASJC Scopus subject areas

  • Neuroscience(all)


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