title: Mg2+ Extrusion from Intestinal Epithelia by CNNM Proteins Is Essential for Gonadogenesis via AMPK-TORC1 Signaling in Caenorhabditis elegans.
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.
authors: Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors: Tasuku
authors: T
authors: Ishii
authors: Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors: Yosuke
authors: Y
authors: Funato
authors: Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors: Osamu
authors: O
authors: Hashizume
authors: Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors: Daisuke
authors: D
authors: Yamazaki
authors: Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
authors: Yusuke
authors: Y
authors: Hirata
authors: Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo, Japan.
authors: Kiyoji
authors: K
authors: Nishiwaki
authors: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.|PRIME, Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo, Japan.
authors: Nozomu
authors: N
authors: Kono
authors: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.|AMED-CREST, Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo, Japan.
authors: Hiroyuki
authors: H
authors: Arai
authors: Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors: Hiroaki
authors: H
authors: Miki
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics*; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics*; D005854:Germ Cells / Q000254:growth & development / Q000378:metabolism; D006066:Gonads / Q000254:growth & development / Q000378:metabolism; D007413:Intestinal Mucosa / Q000254:growth & development / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D008274:Magnesium / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D005810:Multigene Family / Q000235:genetics; D046912:Multiprotein Complexes / Q000235:genetics*; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D027682:Cation Transport Proteins; D016213:Cyclins; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; C510541:AAK-2 protein, C elegans; D055372:AMP-Activated Protein Kinases; D008274:Magnesium