cAMP signalling in mushroom bodies modulates temperature preference behaviour in Drosophila
cAMP signalling in mushroom bodies modulates temperature preference behaviour in Drosophila
复制标题
DOI：
10.1038/nature07090
复制
发表时间：
2008-08-07
期刊：
影响因子：
64.8
通讯作者：
Kim, Jaeseob
中科院分区：
文献类型：
--
作者：
Hong, Sung-Tae;Bang, Sunhoe;Kim, Jaeseob
恒温动物，例如哺乳动物，通过改变代谢率和出汗等生理反应来调节它们的体温。相比之下，变温动物(如果蝇)的体温是与周围环境进行热交换的结果，因为它们的身体表面积与体积的比例很大(1，2)。因此，这些动物必须本能地迁徙到环境温度尽可能接近它们基因决定的理想温度的地方。果蝇本能地偏爱的温度，其作用等同于哺乳动物的“设定温度”。尽管已经发现了各种温度门控Trp通道(3，4)，但果蝇大脑中负责确定所需温度的分子和细胞成分仍然未知。我们通过对果蝇(5，6)的温度偏好行为(TPB)进行大规模遗传筛选来识别这些成分。同时，我们绘制了果蝇大脑控制TPB的区域，方法是用破伤风毒素(7)和由各种大脑特异性GAL4驱动的钾通道(Kir2.1)(8)有针对性地灭活神经元。在这里，我们表明蘑菇小体(MBS)和cAMP-cAMP依赖的蛋白激酶A(cAMP-PKA)途径是控制TPB所必需的。此外，仅在MB中靶向表达cAMP-PKA途径组件就足以挽救相应突变体的异常TPB。在不同的PKA途径突变体中，MBS中cAMP水平和PKA活性影响其偏好温度。
Homoiotherms, for example mammals, regulate their body temperature with physiological responses such as a change of metabolic rate and sweating. In contrast, the body temperature of poikilotherms, for example Drosophila, is the result of heat exchange with the surrounding environment as a result of the large ratio of surface area to volume of their bodies(1,2). Accordingly, these animals must instinctively move to places with an environmental temperature as close as possible to their genetically determined desired temperature. The temperature that Drosophila instinctively prefers has a function equivalent to the 'set point' temperature in mammals. Although various temperature-gated TRP channels have been discovered(3,4), molecular and cellular components in Drosophila brain responsible for determining the desired temperature remain unknown. We identified these components by performing a large-scale genetic screen of temperature preference behaviour (TPB) in Drosophila(5,6). In parallel, we mapped areas of the Drosophila brain controlling TPB by targeted inactivation of neurons with tetanus toxin(7) and a potassium channel (Kir2.1)(8) driven with various brain-specific GAL4s. Here we show that mushroom bodies (MBs) and the cyclic AMP-cAMP-dependent protein kinase A (cAMP-PKA) pathway are essential for controlling TPB. Furthermore, targeted expression of cAMP-PKA pathway components in only the MB was sufficient to rescue abnormal TPB of the corresponding mutants. Preferred temperatures were affected by the level of cAMP and PKA activity in the MBs in various PKA pathway mutants.