RRC ID 53325
著者 Ishii T, Funato Y, Hashizume O, Yamazaki D, Hirata Y, Nishiwaki K, Kono N, Arai H, Miki H.
タイトル Mg2+ Extrusion from Intestinal Epithelia by CNNM Proteins Is Essential for Gonadogenesis via AMPK-TORC1 Signaling in Caenorhabditis elegans.
ジャーナル PLoS Genet
Abstract Mg2+ serves as an essential cofactor for numerous enzymes and its levels are tightly regulated by various Mg2+ transporters. Here, we analyzed Caenorhabditis elegans strains carrying mutations in genes encoding cyclin M (CNNM) Mg2+ transporters. We isolated inactivating mutants for each of the five Caenorhabditis elegans cnnm family genes, cnnm-1 through cnnm-5. cnnm-1; cnnm-3 double mutant worms showed various phenotypes, among which the sterile phenotype was rescued by supplementing the media with Mg2+. This sterility was caused by a gonadogenesis defect with severely attenuated proliferation of germ cells. Using this gonadogenesis defect as an indicator, we performed genome-wide RNAi screening, to search for genes associated with this phenotype. The results revealed that RNAi-mediated inactivation of several genes restores gonad elongation, including aak-2, which encodes the catalytic subunit of AMP-activated protein kinase (AMPK). We then generated triple mutant worms for cnnm-1; cnnm-3; aak-2 and confirmed that the aak-2 mutation also suppressed the defective gonadal elongation in cnnm-1; cnnm-3 mutant worms. AMPK is activated under low-energy conditions and plays a central role in regulating cellular metabolism to adapt to the energy status of cells. Thus, we provide genetic evidence linking Mg2+ homeostasis to energy metabolism via AMPK.
巻・号 12(8)
ページ e1006276
公開日 2016-8-1
DOI 10.1371/journal.pgen.1006276
PII PGENETICS-D-16-00367
PMID 27564576
PMC PMC5001713
MeSH AMP-Activated Protein Kinases Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cation Transport Proteins / genetics* Cyclins / biosynthesis Cyclins / genetics* Germ Cells / growth & development Germ Cells / metabolism Gonads / growth & development Gonads / metabolism Intestinal Mucosa / growth & development Intestinal Mucosa / metabolism Longevity / genetics* Magnesium / metabolism Mechanistic Target of Rapamycin Complex 1 Multigene Family / genetics Multiprotein Complexes / genetics* Mutation Protein Serine-Threonine Kinases / genetics* Protein Serine-Threonine Kinases / metabolism RNA Interference Signal Transduction / genetics TOR Serine-Threonine Kinases / genetics*
IF 5.175
引用数 7
リソース情報
線虫 tm1944