RRC ID 51409
著者 Sinclair J, Pinter K, Samuel T, Beardsley S, Yuan X, Zhang J, Meng K, Yun S, Krause M, Hamza I.
タイトル Inter-organ signalling by HRG-7 promotes systemic haem homeostasis.
ジャーナル Nat Cell Biol
Abstract Growing evidence in vertebrates predicts that cellular haem levels in animals are maintained not only by a cell's internal capacity for haem synthesis in a cell-autonomous manner, but also by an inter-organ haem trafficking network through cell-non-autonomous regulation. Using Caenorhabditis elegans, a genetically and optically amenable animal model for visualizing haem-dependent signalling, we show that HRG-7, a protein with homology to aspartic proteases, mediates inter-organ signalling between the intestine and extra-intestinal tissues. Intestinal HRG-7 functions as a secreted signalling factor during haem starvation in extra-intestinal tissues and is regulated through a DBL-1, homologous to BMP5, dependent signal from neurons. Given the evidence that vertebrate homologues exist for each of the components of the HRG-7-mediated signalling pathway, it is conceivable that the cell-non-autonomous signalling framework that we uncovered in C. elegans may have functional relevance for inter-organ regulation of iron and haem metabolism in humans.
巻・号 19(7)
ページ 799-807
公開日 2017-7-1
DOI 10.1038/ncb3539
PII ncb3539
PMID 28581477
PMC PMC5594749
MeSH Animals Animals, Genetically Modified Biological Transport Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / genetics Carrier Proteins / metabolism Gene Expression Regulation Heme / deficiency Heme / metabolism* Hemeproteins / genetics Hemeproteins / metabolism* Homeostasis Intestinal Mucosa / metabolism* Neurons / metabolism Neuropeptides / genetics Neuropeptides / metabolism RNA Interference Signal Transduction* Time Factors Transcription Factors / genetics Transcription Factors / metabolism Transforming Growth Factor beta / genetics Transforming Growth Factor beta / metabolism
IF 20.042
引用数 8
リソース情報
線虫 tm6801