C. elegans AMPKs promote survival and arrest germline development during nutrient stress.
C. elegans AMPKs promote survival and arrest germline development during nutrient stress.
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DOI：
10.1242/bio.2012836
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发表时间：
2012-10-15
期刊：
影响因子：
2.4
通讯作者：
Katada T
中科院分区：
文献类型：
--
作者：
Fukuyama M;Sakuma K;Park R;Kasuga H;Nagaya R;Atsumi Y;Shimomura Y;Takahashi S;Kajiho H;Rougvie A;Kontani K;Katada T
控制发育、生长和代谢的机制在应对环境条件变化时得到协调，从而提高了存活至生殖成熟的可能性。关于环境对这些过程的影响的分子基础，还有很多东西有待了解。C.线虫幼虫在营养不良的条件下孵化时进入称为L1滞育的发育休眠状态。线虫pten同源物daf-18在此期间对于维持生存和生殖系干细胞静止是必不可少的，但其功能的信号网络的细节仍有待阐明。在这里，我们报告说，动物缺乏aak-1和aak-2，这两个编码AMP激活蛋白激酶（AMPK）的催化α亚基，表现出降低的活力和失败，以维持有丝分裂静止在生殖干细胞在L1滞育。此外，未能阻止生殖系增殖具有长期后果;经历L1滞育的aak双突变体在返回食物时发育成不育成虫，而它们的连续喂养的兄弟姐妹是可育的。aak和daf-18似乎都通过抑制共同下游靶标TORC 1（TOR复合物1）的活性来维持种系静止。相反，拯救的致死表型表明，aak-2的行为不仅在肠道中，daf-18，但也在神经元，可能促进生存，防止能量剥夺L1滞育。这些结果不仅提供了证据表明，AMPK有助于生存在L1滞育的方式不同，它控制dauer滞育，但他们也表明，AMPK抑制TORC 1活性，以维持干细胞静止。
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, 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.
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AMP激活的蛋白激酶对ULK1（HATG1）的磷酸化将能量传感连接到线粒体。
DOI：
10.1126/science.1196371
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Egan DF;Shackelford DB;Mihaylova MM;Gelino S;Kohnz RA;Mair W;Vasquez DS;Joshi A;Gwinn DM;Taylor R;Asara JM;Fitzpatrick J;Dillin A;Viollet B;Kundu M;Hansen M;Shaw RJ
通讯作者：
Shaw RJ
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
11.8
作者：
Brisbin, Sarah;Liu, Jun;Chin-Sang, Ian
通讯作者：
Chin-Sang, Ian
影响因子：
9.7
作者：
Gaur, Shikha;Chen, Linling;Yen, Yun
通讯作者：
Yen, Yun
影响因子：
9.2
作者：
Fukuyama, M;Rougvie, AE;Rothman, JH
通讯作者：
Rothman, JH