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@ARTICLE{Corradini:137502,
author = {Corradini, Eleonora and Vallur, Raghavan and Raaijmakers,
Linsey M and Feil, Susanne and Feil, Robert and Heck, Albert
J R and Scholten, Arjen},
title = {{A}lterations in the cerebellar ({P}hospho)proteome of a
cyclic guanosine monophosphate (c{GMP})-dependent protein
kinase knockout mouse.},
journal = {Molecular $\&$ cellular proteomics},
volume = {13},
number = {8},
issn = {1535-9476},
address = {Bethesda, Md.},
publisher = {The American Society for Biochemistry and Molecular
Biology},
reportid = {DZNE-2020-03824},
pages = {2004-2016},
year = {2014},
abstract = {The cyclic nucleotide cyclic guanosine monophosphate (cGMP)
plays an important role in learning and memory, but its
signaling mechanisms in the mammalian brain are not fully
understood. Using mass-spectrometry-based proteomics, we
evaluated how the cerebellum adapts its (phospho)proteome in
a knockout mouse model of cGMP-dependent protein kinase type
I (cGKI). Our data reveal that a small subset of proteins in
the cerebellum $(∼3\%$ of the quantified proteins) became
substantially differentially expressed in the absence of
cGKI. More changes were observed at the phosphoproteome
level, with hundreds of sites being differentially
phosphorylated between wild-type and knockout cerebellum.
Most of these phosphorylated sites do not represent known
cGKI substrates. An integrative computational network
analysis of the data indicated that the differentially
expressed proteins and proteins harboring differentially
phosphorylated sites largely belong to a tight network in
the Purkinje cells of the cerebellum involving important
cGMP/cAMP signaling nodes (e.g. PDE5 and PKARIIβ) and
Ca(2+) signaling (e.g. SERCA3). In this way, removal of cGKI
could be linked to impaired cerebellar long-term depression
at Purkinje cell synapses. In addition, we were able to
identify a set of novel putative (phospho)proteins to be
considered in this network. Overall, our data improve our
understanding of cerebellar cGKI signaling and suggest novel
players in cGKI-regulated synaptic plasticity.},
keywords = {Animals / Cerebellum: metabolism / Cyclic GMP / Cyclic
GMP-Dependent Protein Kinase Type I: genetics / Cyclic
GMP-Dependent Protein Kinase Type I: metabolism / Mice /
Mice, Knockout / Phosphoproteins: isolation $\&$
purification / Phosphorylation / Proteomics: methods /
Signal Transduction / Synapses: metabolism / Phosphoproteins
(NLM Chemicals) / Cyclic GMP-Dependent Protein Kinase Type I
(NLM Chemicals) / Prkg1 protein, mouse (NLM Chemicals) /
Cyclic GMP (NLM Chemicals)},
cin = {AG N.N. 3},
ddc = {610},
cid = {I:(DE-2719)1240015},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24925903},
pmc = {pmc:PMC4125733},
doi = {10.1074/mcp.M113.035154},
url = {https://pub.dzne.de/record/137502},
}