TY  - JOUR
AU  - Tüshaus, Johanna
AU  - Müller, Stephan A
AU  - Kataka, Evans Sioma
AU  - Zaucha, Jan
AU  - Sebastian Monasor, Laura
AU  - Su, Minhui
AU  - Güner, Gökhan
AU  - Jocher, Georg
AU  - Tahirovic, Sabina
AU  - Frishman, Dmitrij
AU  - Simons, Mikael
AU  - Lichtenthaler, Stefan
TI  - An optimized quantitative proteomics method establishes the cell type-resolved mouse brain secretome.
JO  - The EMBO journal
VL  - 39
IS  - 20
SN  - 1460-2075
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DZNE-2021-00213
SP  - e105693
PY  - 2020
N1  - ISSN 1460-2075 not unique: **3 hits**.
AB  - 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.
KW  - ADAM Proteins: cerebrospinal fluid
KW  - ADAM Proteins: metabolism
KW  - Amyloid Precursor Protein Secretases: antagonists & inhibitors
KW  - Amyloid Precursor Protein Secretases: cerebrospinal fluid
KW  - Amyloid Precursor Protein Secretases: metabolism
KW  - Animals
KW  - Antigens, CD: cerebrospinal fluid
KW  - Antigens, CD: metabolism
KW  - Aspartic Acid Endopeptidases: antagonists & inhibitors
KW  - Aspartic Acid Endopeptidases: cerebrospinal fluid
KW  - Aspartic Acid Endopeptidases: metabolism
KW  - Astrocytes: metabolism
KW  - Brain: cytology
KW  - Brain: metabolism
KW  - Cells, Cultured
KW  - Cerebrospinal Fluid Proteins
KW  - Chromatography, Liquid
KW  - Gene Ontology
KW  - Lipopolysaccharides: pharmacology
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Microglia: metabolism
KW  - Nerve Tissue Proteins: cerebrospinal fluid
KW  - Nerve Tissue Proteins: metabolism
KW  - Neurons: metabolism
KW  - Oligodendroglia: metabolism
KW  - Principal Component Analysis
KW  - Proteome: metabolism
KW  - Proteomics: methods
KW  - Software
KW  - Tandem Mass Spectrometry
KW  -  CSF  (Other)
KW  - BACE1 (Other)
KW  - brain cells (Other)
KW  - proteomics (Other)
KW  - secretomics (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:32954517
C2  - pmc:PMC7560198
DO  - DOI:10.15252/embj.2020105693
UR  - https://pub.dzne.de/record/154360
ER  -