Cholinergic signaling at the body wall neuromuscular junction distally inhibits feeding behavior in Caenorhabditis elegans.

Cholinergic signaling at the body wall neuromuscular junction distally inhibits feeding behavior in Caenorhabditis elegans.
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DOI:
10.1016/j.jbc.2021.101466
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发表时间:
2022-01
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
O'Connor V
O'Connor V
中科院分区:
其他
文献类型:
--
作者:
Izquierdo PG;Calahorro F;Thisainathan T;Atkins JH;Haszczyn J;Lewis CJ;Tattersall JEH;Green AC;Holden-Dye L;O'Connor V

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生物体内复杂的生物功能常常是由组织间的系统交流来协调的。在模式生物秀丽隐杆线虫中,咽部和体壁神经肌肉连接是两个独立的结构,分别控制摄食和运动。单独的,定义明确的神经肌肉回路控制着这些不同的组织。然而,为了保证食物摄取的效率,进食和运动这两个紧急行为是相互协调的。在这里,我们表明胆碱能在体壁肌肉传递的药理学过度激活会降低泵送行为的速率。这是由系统筛选胆碱酯酶抑制剂涕灭威对突变虫咽吸食物率的影响证明的。筛选结果表明,涕灭威对咽泵抑制作用的关键决定因素位于体壁神经肌肉交界处。事实上,用激动剂左旋咪唑选择性刺激体壁肌肉受体以水平1依赖性的方式抑制泵送。有趣的是,这种反应与unc-38无关,unc-38是尼古丁受体的α亚基,通常在体壁肌肉中以1级表达。这意味着一种未表征的含1级受体支撑着这种效应。总之,我们的研究结果表明,体壁胆碱能传递不仅控制运动,同时也抑制摄食行为。
Complex biological functions within organisms are frequently orchestrated by systemic communication between tissues. In the model organism Caenorhabditis elegans, the pharyngeal and body wall neuromuscular junctions are two discrete structures that control feeding and locomotion, respectively. Separate, the well-defined neuromuscular circuits control these distinct tissues. Nonetheless, the emergent behaviors, feeding and locomotion, are coordinated to guarantee the efficiency of food intake. Here, we show that pharmacological hyperactivation of cholinergic transmission at the body wall muscle reduces the rate of pumping behavior. This was evidenced by a systematic screening of the effect of the cholinesterase inhibitor aldicarb on the rate of pharyngeal pumping on food in mutant worms. The screening revealed that the key determinants of the inhibitory effect of aldicarb on pharyngeal pumping are located at the body wall neuromuscular junction. In fact, the selective stimulation of the body wall muscle receptors with the agonist levamisole inhibited pumping in a lev-1-dependent fashion. Interestingly, this response was independent of unc-38, an alpha subunit of the nicotinic receptor classically expressed with lev-1 at the body wall muscle. This implies an uncharacterized lev-1-containing receptor underpins this effect. Overall, our results reveal that body wall cholinergic transmission not only controls locomotion but simultaneously inhibits feeding behavior.
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