Cited by 89Advanced Proteomics Techniques and ApplicationsNeuroinflammation and Neurodegeneration MechanismsAdvanced Biosensing Techniques and Applications

An optimized quantitative proteomics method establishes the cell type‐resolved mouse brain secretome

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Tüshaus, Johanna, Müller, Stephan A, Kataka, Evans Sioma, Zaucha, Jan, Sebastian Monasor, Laura, Su, Minhui, Güner, Gökhan, Jocher, Georg +4 more·2020·The EMBO Journal

Published version of a preprint

Abstract

To understand how cells communicate in the nervous system, it is essential to define their secretome, which is challenging for primary cells because of large cell numbers being required. Here, we miniaturized secretome analysis by developing the “high‐performance secretome protein enrichment with click sugars” (hiSPECS) method. To demonstrate its broad utility, hiSPECS was used to identify the secretory response of brain slices upon LPS‐induced neuroinflammation and to establish the cell type‐resolved mouse brain secretome resource using primary astrocytes, microglia, neurons, and oligodendrocytes. This resource allowed mapping the cellular origin of CSF proteins and revealed that an unexpectedly high number of secreted proteins in vitro and in vivo are proteolytically cleaved membrane protein ectodomains. Two examples are neuronally secreted ADAM22 and CD200, which we identified as substrates of the Alzheimer‐linked protease BACE1. hiSPECS and the brain secretome resource can be widely exploited to systematically study protein secretion and brain function and to identify cell type‐specific biomarkers for CNS diseases.

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Authors
Tüshaus, J., Müller, S. A., Kataka, E. S., Zaucha, J., Sebastian Monasor, L., Su, M., Güner, G., Jocher, G., Tahirovic, S., Frishman, D., Simons, M., & Lichtenthaler, S. F.
Affiliations
  • German Center for Neurodegenerative Diseases (DE)
  • Technical University of Munich (DE)
Corresponding author
Lichtenthaler, Stefan F
Venue
The EMBO Journal
Published
2020-09-21
Volume
39
Issue
20
Pages
e105693-e105693
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W3087614358
Cited by
88
References
64
Citations by year
2026: 11 · 2025: 17 · 2024: 11 · 2023: 14 · 2022: 18 · 2021: 13 · 2020: 4
FWCI
4.68
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion, other-oa)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by)
  • mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
  • DZNE Pub (submittedVersion, cc-by)
Funders
  • Deutsche Forschungsgemeinschaft (EXC 2145 SyNergy project ID 390857198)
  • Bundesministerium für Bildung und Forschung (CLINSPECT‐M and JPND PMG‐AD)
  • Alzheimer Forschung Initiative (18014)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced Biosensing Techniques and Applications
Keywords
mouse brain, primary astrocytes, microglia, neurons, oligodendrocytes, LPS-induced neuroinflammation, cerebrospinal fluid protein, proteolytic cleavage, ADAM22, CD200, BACE1, Alzheimer's disease
MeSH terms
Animals, Astrocytes, Brain, Cells, Cultured, Cerebrospinal Fluid Proteins, Chromatography, Liquid, Lipopolysaccharides, Mice, Inbred C57BL, Nerve Tissue Proteins, Neurons, Oligodendroglia, Software, Antigens, CD, Aspartic Acid Endopeptidases, Microglia, Proteome, Principal Component Analysis, Proteomics, Mice, ADAM Proteins, Tandem Mass Spectrometry, Amyloid Precursor Protein Secretases, Gene Ontology

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