G protein-coupled receptor kinase-2 (GRK-2) controls exploration through neuropeptide signaling in Caenorhabditis elegans.
G protein-coupled receptor kinase-2 (GRK-2) controls exploration through neuropeptide signaling in Caenorhabditis elegans.
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DOI：
10.1371/journal.pgen.1010613
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发表时间：
2023-01
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
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动物会根据环境条件以及它们的发育和代谢状态改变它们的行为方式。例如，秀丽隐杆线虫在幼虫蜕皮或吃饱时是静止的。相比之下，蠕虫在远离食物时进入探索状态。感觉知觉影响秀丽隐杆线虫的运动静止（定义为缺乏身体运动），以及与运动活动增加或减少相关的额外运动状态的表达，如漫游（探索行为）和居住（局部搜索）。我们发现G蛋白偶联受体激酶grk-2突变动物的运动静止增强，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。通过神经元特异性救助实验，我们发现GRK-2在多个纤毛化学感觉神经元中起作用，控制探索行为。grk-2与cgmp依赖性蛋白激酶基因egl-4的作用方式相反，控制运动静止和探索行为。对纤毛感觉神经元缺陷突变体的分析表明，grk-2和纤毛结构突变体在同一途径上控制探索行为。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，我们发现FLP-1神经肽的分泌受到GRK-2的负调控，并且FLP-1的过表达会减少探索行为。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通路。许多调节性神经递质通过与G蛋白偶联受体（gpcr）结合并启动改变神经元活动的信号来影响行为。gpcr受G蛋白偶联受体激酶（GRKs）调控。GRKs磷酸化并促进gpcr失活。在这里，我们确定GRK-2作为秀丽隐杆线虫不同运动状态的调节因子。我们发现GRK-2在嗅觉感觉神经元中促进探索和抑制运动静止。此外，我们发现GRK-2的作用与作用于中间神经元的神经肽信号通路相反。因此，本研究证明了GRK-2在调节神经调节信号和运动行为中的关键作用。
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. Many modulatory neurotransmitters affect behavior by binding to G protein-coupled receptors (GPCRs) and initiating signals that modify neuronal activity. GPCRs are regulated by G protein-coupled receptor kinases (GRKs). GRKs phosphorylate and promote the inactivation of GPCRs. Here we identify GRK-2 as a regulator of distinct locomotor states in C. elegans. We find that GRK-2 acts in olfactory sensory neurons to promote exploration and suppress movement quiescence. Additionally, we show that GRK-2 acts in opposition to a neuropeptide signaling pathway that acts in interneurons. Thus, this study demonstrates critical roles for GRK-2 in regulating neuromodulatory signaling and locomotor behavior.
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影响因子：
3.7
作者：
Buntschuh, Ingrid;Raps, Daniel A.;Li, Chris
通讯作者：
Li, Chris
影响因子：
14.8
作者：
Churgin, Matthew A.;Szuperak, Milan;Kayser, Matthew S.
通讯作者：
Kayser, Matthew S.
影响因子：
11.4
作者：
Hukema, RK;Rademakers, S;Jansen, G
通讯作者：
Jansen, G
DOI：
10.1073/pnas.0409009101
发表时间：
2005-03-01
影响因子：
11.1
作者：
Gray, JM;Hill, JJ;Bargmann, CI
通讯作者：
Bargmann, CI
影响因子：
16.2
作者：
Fujiwara, M;Sengupta, P;McIntire, SL
通讯作者：
McIntire, SL