PXD021869

PXD021869 is an original dataset announced via ProteomeXchange.

Title	Heterozygous mutation of NF-B innate immune response transcription factor Relish increases survival following traumatic brain injury in Drosophila
Description	Traumatic brain injury (TBI) pathologies are caused by primary and secondary injuries. Primary injuries result from physical damage to the brain, and secondary injuries arise from cellular responses to primary injuries. A characteristic cellular response is sustained activation of inflammatory pathways commonly mediated by NF-B transcription factors. Using a Drosophila melanogaster TBI model, we previously found that the main proximal transcriptional response to primary injuries is triggered by activation of Toll and Imd innate immune response pathways that engage NF-B factors Dif and Relish (Rel), respectively. Here, we monitor the abundance of Rel protein by mass spectrometry (MS) and observe that Rel increases in fly heads at 4-8 h after TBI. To investigate the necessity of Rel for secondary injuries, we generated a null allele, Reldel, by CRISPR/Cas9 editing. Heterozygous but not homozygous Reldel mutation reduced mortality at 24 h after TBI and increased the lifespan of injured flies. Additionally, the effect of heterozygous Reldel mutation on mortality was modulated by genetic background and diet. To identify genes that facilitate effects of heterozygous Reldel mutation on TBI outcomes, we compared genome-wide mRNA expression profiles of uninjured and injured +/+, +/Reldel, and Reldel/Reldel flies at 4 h following TBI. Only a few genes changed expression more than two-fold in +/Reldel flies relative to +/+ and Reldel/Reldel flies, and they were not canonical innate immune response genes. Therefore, Rel is necessary for TBI-induced secondary injuries but in complex ways involving Rel gene dose, genetic background, diet, and possibly small changes in expression of innate immune response genes.
HostingRepository	PRIDE
AnnounceDate	2020-12-04
AnnouncementXML	Submission_2020-12-03_23:45:13.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Edna Angelica Trujillo
SpeciesList	scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-07 00:10:58	ID requested
⏵ 1	2020-12-03 23:45:14	announced

Swanson LC, Trujillo EA, Thiede GH, Katzenberger RJ, Shishkova E, Coon JJ, Ganetzky B, Wassarman DA, B Innate Immune Response Transcription Factor Relish. Genetics, 216(4):1117-1136(2020) [pubmed]

submitter keyword: Traumatic Brain Injury, Proteomics, LC-MS/MS, Longitudinal

Joshua J. Coon
contact affiliation	Department of Chemistry, College of Letters & Science, University of Wisconsin-Madison, Madison, WI, 53706 Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53706
contact email	jcoon.wisc.edu@gmail.com
lab head
Edna Angelica Trujillo
contact affiliation	University of Wisconsin Madison
contact email	etrujillo2@wisc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021869
     1. Label: PRIDE project
     2. Name: Heterozygous mutation of NF-B innate immune response transcription factor Relish increases survival following traumatic brain injury in Drosophila