Mg2+ Extrusion from Intestinal Epithelia by CNNM Proteins Is Essential for Gonadogenesis via AMPK-TORC1 Signaling in Caenorhabditis elegans
In: PLoS Genetics, Jg. 12 (2016-08-01), Heft 8
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Zugriff:
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.
Author Summary Mg2+ is the second most abundant cation in cells and serves as an essential cofactor for numerous enzymes. To avoid its shortage, cellular and organismal levels of Mg2+ are tightly regulated by the concerted actions of various Mg2+ transporters and channels. In this study, we analyzed Caenorhabditis elegans strains carrying mutations in genes encoding Mg2+ transporters and found that the mutations abrogated Mg2+ homeostasis. Additionally, these worms were sterile because of a developmental defect in the gonads with severely attenuated proliferation of germ cells. These abnormalities were rescued by additional Mg2+ supplementation to the medium, and thus were considered to be due to Mg2+ shortage. We investigated the mechanism of this Mg2+-associated attenuation of gonadal development, and found that disrupting of the function of AMP-activated protein kinase (AMPK) restored gonad elongation. It is well-known that 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 demonstrated that Mg2+ homeostasis is intimately connected to energy metabolism via AMPK.
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Mg2+ Extrusion from Intestinal Epithelia by CNNM Proteins Is Essential for Gonadogenesis via AMPK-TORC1 Signaling in Caenorhabditis elegans
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Autor/in / Beteiligte Person: | Kono, Nozomu ; Miki, Hiroaki ; Nishiwaki, Kiyoji ; Arai, Hiroyuki ; Hashizume, Osamu ; Hirata, Yusuke ; Ishii, Tasuku ; Funato, Yosuke ; Yamazaki, Daisuke |
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Zeitschrift: | PLoS Genetics, Jg. 12 (2016-08-01), Heft 8 |
Veröffentlichung: | Public Library of Science, 2016 |
Medientyp: | unknown |
ISSN: | 1553-7404 (print) ; 1553-7390 (print) |
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