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

Johanna Tüshaus, Stephan A. Müller, Evans Sioma Kataka, Jan Zaucha, Laura Sebastian Monasor, Minhui Su, Gökhan Güner, Georg Jocher, Sabina Tahirovic, Dmitrij Frishman, Mikael Simons, Stefan F. Lichtenthaler

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

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.

Original languageEnglish
Article numbere105693
JournalEMBO Journal
Volume39
Issue number20
DOIs
StatePublished - 15 Oct 2020

Keywords

  • BACE1
  • CSF
  • brain cells
  • proteomics
  • secretomics

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