C. elegans AMPKs promote survival and arrest germline development during nutrient stress
Summary Mechanisms controlling development, growth, and metabolism are coordinated in response to changes in environmental conditions, enhancing the likelihood of survival to reproductive maturity. Much remains to be learned about the molecular basis underlying environmental influences on these proc...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2012-08-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/1/10/929 |
| _version_ | 1818859794854838272 |
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| author | Masamitsu Fukuyama Kensuke Sakuma Riyong Park Hidefumi Kasuga Ryotaro Nagaya Yuriko Atsumi Yumi Shimomura Shinya Takahashi Hiroaki Kajiho Ann Rougvie Kenji Kontani Toshiaki Katada |
| author_facet | Masamitsu Fukuyama Kensuke Sakuma Riyong Park Hidefumi Kasuga Ryotaro Nagaya Yuriko Atsumi Yumi Shimomura Shinya Takahashi Hiroaki Kajiho Ann Rougvie Kenji Kontani Toshiaki Katada |
| author_sort | Masamitsu Fukuyama |
| collection | DOAJ |
| description | Summary
Mechanisms controlling development, growth, and metabolism are coordinated in response to changes in environmental conditions, enhancing the likelihood of survival to reproductive maturity. Much remains to be learned about the molecular basis underlying environmental influences on these processes. C. elegans larvae enter a developmentally dormant state called L1 diapause when hatched into nutrient-poor conditions. The nematode pten homologue daf-18 is essential for maintenance of survival and germline stem cell quiescence during this period (Fukuyama et al., 2006; Sigmond et al., 2008), but the details of the signaling network(s) in which it functions remain to be elucidated. Here, we report that animals lacking both aak-1 and aak-2, which encode the two catalytic α subunits of AMP-activated protein kinase (AMPK), show reduced viability and failure to maintain mitotic quiescence in germline stem cells during L1 diapause. Furthermore, failure to arrest germline proliferation has a long term consequence; aak double mutants that have experienced L1 diapause develop into sterile adults when returned to food, whereas their continuously fed siblings are fertile. Both aak and daf-18 appear to maintain germline quiescence by inhibiting activity of the common downstream target, TORC1 (TOR Complex 1). In contrast, rescue of the lethality phenotype indicates that aak-2 acts not only in the intestine, as does daf-18, but also in neurons, likely promoting survival by preventing energy deprivation during L1 diapause. These results not only provide evidence that AMPK contributes to survival during L1 diapause in a manner distinct from that by which it controls dauer diapause, but they also suggest that AMPK suppresses TORC1 activity to maintain stem cell quiescence. |
| first_indexed | 2024-12-19T09:17:50Z |
| format | Article |
| id | doaj.art-7f91c3d7b9d5460a8724a09f5751566c |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-19T09:17:50Z |
| publishDate | 2012-08-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-7f91c3d7b9d5460a8724a09f5751566c2022-12-21T20:28:04ZengThe Company of BiologistsBiology Open2046-63902012-08-0111092993610.1242/bio.20128362012836C. elegans AMPKs promote survival and arrest germline development during nutrient stressMasamitsu Fukuyama0Kensuke Sakuma1Riyong Park2Hidefumi Kasuga3Ryotaro Nagaya4Yuriko Atsumi5Yumi Shimomura6Shinya Takahashi7Hiroaki Kajiho8Ann Rougvie9Kenji Kontani10Toshiaki Katada11 Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 113-0033, Japan Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 113-0033, Japan Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 113-0033, Japan Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 113-0033, Japan Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 113-0033, Japan Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 113-0033, Japan Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 113-0033, Japan Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 113-0033, Japan Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 113-0033, Japan Department of Genetics, Cell Biology and Development, University of Minnesota, MN 55455, USA Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 113-0033, Japan Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 113-0033, Japan Summary Mechanisms controlling development, growth, and metabolism are coordinated in response to changes in environmental conditions, enhancing the likelihood of survival to reproductive maturity. Much remains to be learned about the molecular basis underlying environmental influences on these processes. C. elegans larvae enter a developmentally dormant state called L1 diapause when hatched into nutrient-poor conditions. The nematode pten homologue daf-18 is essential for maintenance of survival and germline stem cell quiescence during this period (Fukuyama et al., 2006; Sigmond et al., 2008), but the details of the signaling network(s) in which it functions remain to be elucidated. Here, we report that animals lacking both aak-1 and aak-2, which encode the two catalytic α subunits of AMP-activated protein kinase (AMPK), show reduced viability and failure to maintain mitotic quiescence in germline stem cells during L1 diapause. Furthermore, failure to arrest germline proliferation has a long term consequence; aak double mutants that have experienced L1 diapause develop into sterile adults when returned to food, whereas their continuously fed siblings are fertile. Both aak and daf-18 appear to maintain germline quiescence by inhibiting activity of the common downstream target, TORC1 (TOR Complex 1). In contrast, rescue of the lethality phenotype indicates that aak-2 acts not only in the intestine, as does daf-18, but also in neurons, likely promoting survival by preventing energy deprivation during L1 diapause. These results not only provide evidence that AMPK contributes to survival during L1 diapause in a manner distinct from that by which it controls dauer diapause, but they also suggest that AMPK suppresses TORC1 activity to maintain stem cell quiescence.http://bio.biologists.org/content/1/10/929AMPKStem cellDiapause |
| spellingShingle | Masamitsu Fukuyama Kensuke Sakuma Riyong Park Hidefumi Kasuga Ryotaro Nagaya Yuriko Atsumi Yumi Shimomura Shinya Takahashi Hiroaki Kajiho Ann Rougvie Kenji Kontani Toshiaki Katada C. elegans AMPKs promote survival and arrest germline development during nutrient stress Biology Open AMPK Stem cell Diapause |
| title | C. elegans AMPKs promote survival and arrest germline development during nutrient stress |
| title_full | C. elegans AMPKs promote survival and arrest germline development during nutrient stress |
| title_fullStr | C. elegans AMPKs promote survival and arrest germline development during nutrient stress |
| title_full_unstemmed | C. elegans AMPKs promote survival and arrest germline development during nutrient stress |
| title_short | C. elegans AMPKs promote survival and arrest germline development during nutrient stress |
| title_sort | c elegans ampks promote survival and arrest germline development during nutrient stress |
| topic | AMPK Stem cell Diapause |
| url | http://bio.biologists.org/content/1/10/929 |
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