Journal Article

DZNE-2020-03209

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Label-free quantitative analysis of the membrane proteome of Bace1 protease knock-out zebrafish brains.

Hogl, S. (First author)DZNE* ; van Bebber, F.DZNE* ; Dislich, B.DZNE* ; Kuhn, P.-H.DZNE* ; Haass, C.DZNE* ; Schmid, B.DZNE* ; Lichtenthaler, S. F. (Last author)DZNE*

2013
Wiley VCH69157 Weinheim

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Please use a persistent id in citations: doi:10.1002/pmic.201200582

Abstract: The aspartyl protease BACE1 cleaves neuregulin 1 and is involved in myelination and is a candidate drug target for Alzheimer's disease, where it acts as the β-secretase cleaving the amyloid precursor protein. However, little is known about other substrates in vivo. Here, we provide a proteomic workflow for BACE1 substrate identification from whole brains, combining filter-aided sample preparation, strong-anion exchange fractionation, and label-free quantification. We used bace1-deficient zebrafish and quantified differences in protein levels between wild-type and bace1 -/- zebrafish brains. Over 4500 proteins were identified with at least two unique peptides and quantified in both wild-type and bace1 -/- zebrafish brains. The majority of zebrafish membrane proteins did not show altered protein levels, indicating that Bace1 has a restricted substrate specificity. Twenty-four membrane proteins accumulated in the bace1 -/- brains and thus represent candidate Bace1 substrates. They include several known BACE1 substrates, such as the zebrafish homologs of amyloid precursor protein and the cell adhesion protein L1, which validate the proteomic workflow. Additionally, several candidate substrates with a function in neurite outgrowth and axon guidance, such as plexin A3 and glypican-1 were identified, pointing to a function of Bace1 in neurodevelopment. Taken together, our study provides the first proteomic analysis of knock-out zebrafish tissue and demonstrates that combining gene knock-out models in zebrafish with quantitative proteomics is a powerful approach to address biomedical questions.

Keyword(s): Amyloid beta-Protein Precursor: genetics (MeSH) ; Amyloid beta-Protein Precursor: metabolism (MeSH) ; Animals (MeSH) ; Animals, Genetically Modified (MeSH) ; Aspartic Acid Endopeptidases: genetics (MeSH) ; Aspartic Acid Endopeptidases: metabolism (MeSH) ; Brain: metabolism (MeSH) ; Chemical Fractionation: methods (MeSH) ; Glypicans: metabolism (MeSH) ; Humans (MeSH) ; Membrane Proteins: analysis (MeSH) ; Membrane Proteins: genetics (MeSH) ; Membrane Proteins: metabolism (MeSH) ; Proteome: genetics (MeSH) ; Proteome: metabolism (MeSH) ; Receptors, Cell Surface: metabolism (MeSH) ; Tandem Mass Spectrometry (MeSH) ; Workflow (MeSH) ; Zebrafish: genetics (MeSH) ; Zebrafish: metabolism (MeSH) ; Zebrafish Proteins: analysis (MeSH) ; Zebrafish Proteins: genetics (MeSH) ; Zebrafish Proteins: metabolism (MeSH) ; Amyloid beta-Protein Precursor ; Glypicans ; Membrane Proteins ; Plxna3 protein, zebrafish ; Proteome ; Receptors, Cell Surface ; Zebrafish Proteins ; Aspartic Acid Endopeptidases

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Contributing Institute(s):

1. Neuroproteomics (AG Lichtenthaler)
2. ALS, FTLD and Zebrafish models (AG Haass old)
3. Zebrafish Models (Zebrafish Models ; AG Schmid ; AG Schmid München)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2013

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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