Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Center for Excellence in Environmental Toxicology (CEET), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
PLoS Genet. 2023 Jan 18;19(1):e1010613. doi: 10.1371/journal.pgen.1010613. eCollection 2023 Jan.
Animals alter their behavior in manners that depend on environmental conditions as well as their developmental and metabolic states. For example, C. elegans is quiescent during larval molts or during conditions of satiety. By contrast, worms enter an exploration state when removed from food. Sensory perception influences movement quiescence (defined as a lack of body movement), as well as the expression of additional locomotor states in C. elegans that are associated with increased or reduced locomotion activity, such as roaming (exploration behavior) and dwelling (local search). Here we find that movement quiescence is enhanced, and exploration behavior is reduced in G protein-coupled receptor kinase grk-2 mutant animals. grk-2 was previously shown to act in chemosensation, locomotion, and egg-laying behaviors. Using neuron-specific rescuing experiments, we show that GRK-2 acts in multiple ciliated chemosensory neurons to control exploration behavior. grk-2 acts in opposite ways from the cGMP-dependent protein kinase gene egl-4 to control movement quiescence and exploration behavior. Analysis of mutants with defects in ciliated sensory neurons indicates that grk-2 and the cilium-structure mutants act in the same pathway to control exploration behavior. We find that GRK-2 controls exploration behavior in an opposite manner from the neuropeptide receptor NPR-1 and the neuropeptides FLP-1 and FLP-18. Finally, we show that secretion of the FLP-1 neuropeptide is negatively regulated by GRK-2 and that overexpression of FLP-1 reduces exploration behavior. These results define neurons and molecular pathways that modulate movement quiescence and exploration behavior.
动物会根据环境条件以及其发育和代谢状态改变行为方式。例如，秀丽隐杆线虫在幼虫蜕皮或饱食时处于静止状态。相比之下，当从食物中取出时，蠕虫会进入探索状态。感觉感知会影响运动静止（定义为缺乏身体运动），以及秀丽隐杆线虫中与增加或减少运动活动相关的其他运动状态的表达，例如漫游（探索行为）和居住（局部搜索）。在这里，我们发现运动静止增强，并且 G 蛋白偶联受体激酶 grk-2 突变体动物的探索行为减少。grk-2 先前被证明在化学感觉、运动和产卵行为中起作用。使用神经元特异性挽救实验，我们表明 GRK-2 在多个纤毛化学感觉神经元中起作用以控制探索行为。grk-2 以与 cGMP 依赖性蛋白激酶基因 egl-4 相反的方式作用，以控制运动静止和探索行为。对具有纤毛感觉神经元缺陷的突变体的分析表明，grk-2 和纤毛结构突变体以相同的途径作用以控制探索行为。我们发现 GRK-2 以与神经肽受体 NPR-1 和神经肽 FLP-1 和 FLP-18 相反的方式控制探索行为。最后，我们表明 FLP-1 神经肽的分泌受 GRK-2 负调控，并且 FLP-1 的过表达减少探索行为。这些结果定义了调节运动静止和探索行为的神经元和分子途径。
