Inhibition of germline proliferation during C-elegans dauer development requires PTEN, LKB1 and AMPK signalling
Inhibition of germline proliferation during C-elegans dauer development requires PTEN, LKB1 and AMPK signalling
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DOI：
10.1242/dev.02232
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发表时间：
2006-02-01
期刊：
影响因子：
4.6
通讯作者：
Roy, R
中科院分区：
文献类型：
--
作者：
Narbonne, P;Roy, R
在线虫中，胰岛素样信号传导减少诱导发育静止、生殖延迟和寿命延长。我们在这里表明，LKB 1和AMPK的直向同源线虫在减少胰岛素样信号传导的条件下合作，以建立生殖系干细胞群中的细胞周期静止，除了延长寿命。任一蛋白的失活导致滞育样“dauer”发育期间的异常生殖细胞增殖，而AMPK的丧失使发育停滞与寿命延长分离。TGF-β活性降低也会触发独立于胰岛素样途径的发育静止。我们的数据表明，这两个信号通路会聚在C。在dauer形成过程中，通过AMPK及其上游激活剂LKB 1的调节，而不是通过典型的胰岛素样信号级联，elegans PTEN直系同源物协调种系增殖与体细胞发育。在人类中，TGF-β家族成员、PTEN或LKB 1的种系突变导致相关的肿瘤易感综合征。我们的研究结果建立了一个发展的关系，可能会强调他们的共同的，特有的病因。
In C elegans, reduced insulin-like signalling induces developmental quiescence, reproductive delay and lifespan extension. We show here that the C elegans orthologues of LKB1 and AMPK cooperate during conditions of reduced insulin-like signalling to establish cell cycle quiescence in the germline stem cell population, in addition to prolonging lifespan. The inactivation of either protein causes aberrant germline proliferation during diapause-like 'dauer' development, whereas the loss of AMPK uncouples developmental arrest from lifespan extension. Reduced TGF-beta activity also triggers developmental quiescence independent of the insulin-like pathway. Our data suggest that these two signalling pathways converge on the C. elegans PTEN orthologue to coordinate germline proliferation with somatic development during dauer formation, via the regulation of AMPK and its upstream activator LKB1, rather than through the canonical insulin-like signalling cascade. In humans, germline mutations in TGF-beta family members, PTEN or LKB1 result in related tumour-predisposing syndromes. Our findings establish a developmental relationship that may underscore their shared, characteristic aetiology.