RRC ID 46203
著者 Staab TA, Evgrafov O, Knowles JA, Sieburth D.
タイトル Regulation of synaptic nlg-1/neuroligin abundance by the skn-1/Nrf stress response pathway protects against oxidative stress.
ジャーナル PLoS Genet
Abstract The Nrf family of transcription factors mediates adaptive responses to stress and longevity, but the identities of the crucial Nrf targets, and the tissues in which they function in multicellular organisms to promote survival, are not known. Here, we use whole transcriptome RNA sequencing to identify 810 genes whose expression is controlled by the SKN-1/Nrf2 negative regulator WDR-23 in the nervous system of Caenorhabditis elegans. Among the genes identified is the synaptic cell adhesion molecule nlg-1/neuroligin. We find that the synaptic abundance of NLG-1 protein increases following pharmacological treatments that generate oxidative stress or by the genetic activation of skn-1. Increasing nlg-1 dosage correlates with increased survival in response to oxidative stress, whereas genetic inactivation of nlg-1 reduces survival and impairs skn-1-mediated stress resistance. We identify a canonical SKN-1 binding site in the nlg-1 promoter that binds to SKN-1 in vitro and is necessary for SKN-1 and toxin-mediated increases in nlg-1 expression in vivo. Together, our results suggest that SKN-1 activation in the nervous system can confer protection to organisms in response to stress by directly regulating nlg-1/neuroligin expression.
巻・号 10(1)
ページ e1004100
公開日 2014-1-1
DOI 10.1371/journal.pgen.1004100
PII PGENETICS-D-13-02003
PMID 24453991
PMC PMC3894169
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / biosynthesis Caenorhabditis elegans Proteins / genetics* Cell Adhesion Molecules, Neuronal / biosynthesis Cell Adhesion Molecules, Neuronal / genetics* Cell Survival DNA-Binding Proteins / biosynthesis DNA-Binding Proteins / genetics* Gene Expression Regulation, Developmental Longevity / genetics* Nervous System / growth & development Oxidative Stress / genetics* Promoter Regions, Genetic Transcription Factors / biosynthesis Transcription Factors / genetics* Transcription, Genetic* Transcriptional Activation / genetics
IF 5.175
引用数 25
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm1817 tm1108