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Intercellular signaling by ectodomain shedding at the synapse.

M Dolores Martín-de-Saavedra1, Marc Dos Santos2, Peter Penzes3

  • 1Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, 60611, IL, USA; Instituto Universitario de Investigación en Neuroquímica, Department of Biochemistry and Molecular Biology, School of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain.

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Ectodomain shedding (ES) releases peptides from synaptic proteins, mediating cell signaling. Analyzing shed proteins in cerebrospinal fluid (CSF) may reveal biomarkers for brain disorders.

Keywords:
autismneurodegenerationplasticityproteomicssheddomesynapse

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Ectodomain shedding (ES) is a crucial post-translational modification impacting cellular functions.
  • Synaptic proteins undergo ES, but the roles of shed peptides in signaling are emerging.
  • Understanding ES is vital for comprehending neurological health and disease.

Purpose of the Study:

  • To review evidence of synaptic ES mediating autocrine and paracrine signaling.
  • To highlight the role of proteomics in identifying novel ES substrates and functions.
  • To explore the potential of cerebrospinal fluid (CSF) biomarkers for neuropsychiatric disorders.

Main Methods:

  • Literature review of emerging evidence on synaptic ES.
  • Discussion of advances in large-scale proteomic analyses.
  • Overview of cerebrospinal fluid (CSF) analysis for biomarker discovery.

Main Results:

  • Synaptic ES facilitates autocrine and paracrine signaling pathways.
  • Proteomics enables identification of new proteins undergoing ES and their functions.
  • CSF analysis shows promise for detecting shed proteins as biomarkers.

Conclusions:

  • Synaptic ES is a key regulator of neuronal communication.
  • Proteomic insights are expanding the understanding of ES functions.
  • CSF-based biomarkers derived from shed proteins offer potential for neuropsychiatric disorder diagnosis.