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@ARTICLE{Hogl:136887,
author = {Hogl, Sebastian and van Bebber, Frauke and Dislich, Bastian
and Kuhn, Peer-Hendrik and Haass, Christian and Schmid,
Bettina and Lichtenthaler, Stefan F},
title = {{L}abel-free quantitative analysis of the membrane proteome
of {B}ace1 protease knock-out zebrafish brains.},
journal = {Practical proteomics},
volume = {13},
number = {9},
issn = {1615-9853},
address = {Weinheim},
publisher = {Wiley VCH69157},
reportid = {DZNE-2020-03209},
pages = {1519-1527},
year = {2013},
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.},
keywords = {Amyloid beta-Protein Precursor: genetics / Amyloid
beta-Protein Precursor: metabolism / Animals / Animals,
Genetically Modified / Aspartic Acid Endopeptidases:
genetics / Aspartic Acid Endopeptidases: metabolism / Brain:
metabolism / Chemical Fractionation: methods / Glypicans:
metabolism / Humans / Membrane Proteins: analysis / Membrane
Proteins: genetics / Membrane Proteins: metabolism /
Proteome: genetics / Proteome: metabolism / Receptors, Cell
Surface: metabolism / Tandem Mass Spectrometry / Workflow /
Zebrafish: genetics / Zebrafish: metabolism / Zebrafish
Proteins: analysis / Zebrafish Proteins: genetics /
Zebrafish Proteins: metabolism / Amyloid beta-Protein
Precursor (NLM Chemicals) / Glypicans (NLM Chemicals) /
Membrane Proteins (NLM Chemicals) / Plxna3 protein,
zebrafish (NLM Chemicals) / Proteome (NLM Chemicals) /
Receptors, Cell Surface (NLM Chemicals) / Zebrafish Proteins
(NLM Chemicals) / Aspartic Acid Endopeptidases (NLM
Chemicals)},
cin = {AG Lichtenthaler / AG Haass old / Zebrafish Models ; AG
Schmid ; AG Schmid München},
ddc = {540},
cid = {I:(DE-2719)1110006 / I:(DE-2719)1110007 /
I:(DE-2719)1140002},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:23457027},
doi = {10.1002/pmic.201200582},
url = {https://pub.dzne.de/record/136887},
}