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An optimized quantitative proteomics method establishes the cell type‐resolved mouse brain secretome
Author(s) -
Tüshaus Johanna,
Müller Stephan A,
Kataka Evans Sioma,
Zaucha Jan,
Sebastian Monasor Laura,
Su Minhui,
Güner Gökhan,
Jocher Georg,
Tahirovic Sabina,
Frishman Dmitrij,
Simons Mikael,
Lichtenthaler Stefan F
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020105693
Subject(s) - biology , proteomics , quantitative proteomics , computational biology , brain cell , cell type , microbiology and biotechnology , cell , genetics , gene
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” (hi SPECS ) method. To demonstrate its broad utility, hi SPECS 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 ADAM 22 and CD 200, which we identified as substrates of the Alzheimer‐linked protease BACE 1. hi SPECS 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.