PXD051147-1

PXD051147 is an original dataset announced via ProteomeXchange.

Title	CAP1-KO E18.5 mouCAP1-KO E18.5 mouse cerebral cortices LC-MSMS
Description	Serum response factor (SRF) is a ubiquitously expressed transcription factor that is essential for brain development and function. SRF activity is controlled by two competing classes of coactivators, myocardin-related transcription factors (MRTF) and ternary complex factors, which introduce specificity into gene expression programs. Here, we explored the MRTF-mediated regulatory mechanism in mouse cortical neurons. Using gene-reporter assays and pharmacological and genetic approaches in isolated mouse cortical neurons, we found that cyclase-associated protein 1 (CAP1) repressed neuronal MRTF-SRF activity. CAP1 promoted cytosolic retention of MRTF by controlling cytosolic G-actin levels that required its helical folded domain and its CARP domain. This function of CAP1 was not redundant with that of its homolog CAP2 and was independent of cofilin1 and actin-depolymerizing factor. Deep RNA sequencing and mass spectrometry in cerebral cortex lysates from CAP1 knockout (CAP1-KO) mice supported the in vivo relevance for the CAP1-actin-MRTF-SRF signalling axis. Our study identified CAP1 as a repressor of neuronal gene expression and led to the identification of likely MRTF-SRF target genes in the developing cerebral cortex, whose dysregulation may contribute to impaired formation of neuronal networks in CAP1-KO mice. Together with our previous studies that implicated CAP1 in actin dynamics in axonal growth cones or excitatory synapses, we established CAP1 as a crucial actin regulator in neurons.
HostingRepository	PRIDE
AnnounceDate	2025-01-14
AnnouncementXML	Submission_2025-01-14_01:26:10.856.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Uwe Linne
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-02 03:59:59	ID requested
⏵ 1	2025-01-14 01:26:11	announced

10.1126/scisignal.adj0032;

Khudayberdiev S, Weiss K, Heinze A, Colombaretti D, Trausch N, Linne U, Rust MB, The actin-binding protein CAP1 represses MRTF-SRF-dependent gene expression in mouse cerebral cortex. Sci Signal, 17(835):eadj0032(2024) [pubmed]

submitter keyword: MRTF, embryo, knock-out, brain, actin, SRF, cortex,Cyclase-associated protein 1

Uwe Linne
contact affiliation	Philipps University Marburg Faculty of Chemistry Core Facility for Mass Spectrometry Hans-Meerwein-Str. 4 35032 Marburg GERMANY
contact email	linneu@staff.uni-marburg.de
lab head
Uwe Linne
contact affiliation	Head of Core Facility Mass Spectrometry, Faculty of Chemistry, Philipps-University Marburg
contact email	linneu@staff.uni-marburg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051147
     1. Label: PRIDE project
     2. Name: CAP1-KO E18.5 mouCAP1-KO E18.5 mouse cerebral cortices LC-MSMS