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000154360 0247_ $$2doi$$a10.15252/embj.2020105693
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000154360 037__ $$aDZNE-2021-00213
000154360 041__ $$aEnglish
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000154360 1001_ $$0P:(DE-2719)2812852$$aTüshaus, Johanna$$b0$$eFirst author$$udzne
000154360 245__ $$aAn optimized quantitative proteomics method establishes the cell type-resolved mouse brain secretome.
000154360 260__ $$aHoboken, NJ [u.a.]$$bWiley$$c2020
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000154360 520__ $$aTo 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.
000154360 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000154360 536__ $$0G:(DE-HGF)POF3-341$$a341 - Molecular Signaling (POF3-341)$$cPOF3-341$$fPOF III$$x1
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000154360 650_7 $$2Other$$a CSF 
000154360 650_7 $$2Other$$aBACE1
000154360 650_7 $$2Other$$abrain cells
000154360 650_7 $$2Other$$aproteomics
000154360 650_7 $$2Other$$asecretomics
000154360 650_2 $$2MeSH$$aADAM Proteins: cerebrospinal fluid
000154360 650_2 $$2MeSH$$aADAM Proteins: metabolism
000154360 650_2 $$2MeSH$$aAmyloid Precursor Protein Secretases: antagonists & inhibitors
000154360 650_2 $$2MeSH$$aAmyloid Precursor Protein Secretases: cerebrospinal fluid
000154360 650_2 $$2MeSH$$aAmyloid Precursor Protein Secretases: metabolism
000154360 650_2 $$2MeSH$$aAnimals
000154360 650_2 $$2MeSH$$aAntigens, CD: cerebrospinal fluid
000154360 650_2 $$2MeSH$$aAntigens, CD: metabolism
000154360 650_2 $$2MeSH$$aAspartic Acid Endopeptidases: antagonists & inhibitors
000154360 650_2 $$2MeSH$$aAspartic Acid Endopeptidases: cerebrospinal fluid
000154360 650_2 $$2MeSH$$aAspartic Acid Endopeptidases: metabolism
000154360 650_2 $$2MeSH$$aAstrocytes: metabolism
000154360 650_2 $$2MeSH$$aBrain: cytology
000154360 650_2 $$2MeSH$$aBrain: metabolism
000154360 650_2 $$2MeSH$$aCells, Cultured
000154360 650_2 $$2MeSH$$aCerebrospinal Fluid Proteins
000154360 650_2 $$2MeSH$$aChromatography, Liquid
000154360 650_2 $$2MeSH$$aGene Ontology
000154360 650_2 $$2MeSH$$aLipopolysaccharides: pharmacology
000154360 650_2 $$2MeSH$$aMice
000154360 650_2 $$2MeSH$$aMice, Inbred C57BL
000154360 650_2 $$2MeSH$$aMicroglia: metabolism
000154360 650_2 $$2MeSH$$aNerve Tissue Proteins: cerebrospinal fluid
000154360 650_2 $$2MeSH$$aNerve Tissue Proteins: metabolism
000154360 650_2 $$2MeSH$$aNeurons: metabolism
000154360 650_2 $$2MeSH$$aOligodendroglia: metabolism
000154360 650_2 $$2MeSH$$aPrincipal Component Analysis
000154360 650_2 $$2MeSH$$aProteome: metabolism
000154360 650_2 $$2MeSH$$aProteomics: methods
000154360 650_2 $$2MeSH$$aSoftware
000154360 650_2 $$2MeSH$$aTandem Mass Spectrometry
000154360 7001_ $$0P:(DE-2719)2810938$$aMüller, Stephan A$$b1$$udzne
000154360 7001_ $$0P:(DE-HGF)0$$aKataka, Evans Sioma$$b2
000154360 7001_ $$0P:(DE-HGF)0$$aZaucha, Jan$$b3
000154360 7001_ $$0P:(DE-2719)2812269$$aSebastian Monasor, Laura$$b4$$udzne
000154360 7001_ $$0P:(DE-2719)2813907$$aSu, Minhui$$b5$$udzne
000154360 7001_ $$0P:(DE-2719)2812025$$aGüner, Gökhan$$b6$$udzne
000154360 7001_ $$0P:(DE-2719)2813355$$aJocher, Georg$$b7$$udzne
000154360 7001_ $$0P:(DE-2719)2442036$$aTahirovic, Sabina$$b8$$udzne
000154360 7001_ $$0P:(DE-HGF)0$$aFrishman, Dmitrij$$b9
000154360 7001_ $$0P:(DE-2719)2811642$$aSimons, Mikael$$b10$$udzne
000154360 7001_ $$0P:(DE-2719)2181459$$aLichtenthaler, Stefan$$b11$$eLast author$$udzne
000154360 773__ $$0PERI:(DE-600)1467419-1$$a10.15252/embj.2020105693$$gVol. 39, no. 20$$n20$$pe105693$$tThe EMBO journal$$v39$$x1460-2075$$y2020
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