Lans Hannes, Jansen Gert
MGC Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus MC, 3000 CA Rotterdam, The Netherlands.
Dev Biol. 2007 Mar 15;303(2):474-82. doi: 10.1016/j.ydbio.2006.11.028. Epub 2006 Nov 22.
The life span of the nematode Caenorhabditis elegans is under control of sensory signals detected by the amphid neurons. In these neurons, C. elegans expresses at least 13 Galpha subunits and a Ggamma subunit, which are involved in the transduction and modulation of sensory signals. Here, we show that loss-of-function mutations in the Galpha subunits odr-3, gpa-1 and gpa-9, in the Ggamma subunit gpc-1 and the introduction of extra copies of the Galpha subunit gpa-11 extend the life span of C. elegans. Loss-of-function of odr-3 and extra copies of gpa-11 act synergistically and can together extend life span more than two-fold, indicating that sensory signals play an important role in regulating life span. We show that gpa-1, gpa-11, odr-3 and gpc-1 all signal via the daf-16 FOXO family transcription factor. In addition, odr-3 and gpa-11 might suppress life span extension partially independent of the insulin/IGF-1 like receptor homologue daf-2. Our results suggest that the previously unanticipated nociceptive ASH and/or ADL neurons regulate longevity. We expect that the implication of specific G proteins will eventually contribute to the identification of the sensory cues that determine the rate of aging in C. elegans.
线虫秀丽隐杆线虫的寿命受两性感觉神经元检测到的感觉信号控制。在这些神经元中,秀丽隐杆线虫表达至少13种Gα亚基和1种Gγ亚基,它们参与感觉信号的转导和调节。在此,我们表明,Gα亚基odr-3、gpa-1和gpa-9、Gγ亚基gpc-1的功能丧失突变以及Gα亚基gpa-11额外拷贝的引入延长了秀丽隐杆线虫的寿命。odr-3功能丧失和gpa-11额外拷贝协同作用,可共同将寿命延长两倍以上,表明感觉信号在调节寿命中起重要作用。我们表明,gpa-1、gpa-11、odr-3和gpc-1均通过daf-16 FOXO家族转录因子发出信号。此外,odr-3和gpa-11可能部分独立于胰岛素/IGF-1样受体同源物daf-2抑制寿命延长。我们的结果表明,先前未预料到的伤害感受性ASH和/或ADL神经元调节寿命。我们预计,特定G蛋白的作用最终将有助于确定决定秀丽隐杆线虫衰老速度的感觉线索。