Sharabi Kfir, Charar Chayki, Gruenbaum Yosef
Department of Genetics; Institute of Life Sciences ; Hebrew University of Jerusalem ; Jerusalem, Israel.
Worm. 2015 Jan 28;4(1):e1008898. doi: 10.1080/21624054.2015.1008898. eCollection 2015 Jan-Mar.
Carbon dioxide (CO2) is a key molecule in many biological processes. Studies in humans, mice, D. melanogaster, C. elegans, unicellular organisms and plants have shed light on the molecular pathways activated by elevated levels of CO2. However, the mechanisms that organisms use to sense and respond to high CO2 levels remain largely unknown. Previous work has shown that C. elegans quickly avoid elevated CO2 levels using mechanisms that involve the BAG, ASE and AFD neurons via cGMP- and calcium- signaling pathways. Here, we discuss our recent finding that exposure of C. elegans to high CO2 levels leads to a very rapid cessation in the contraction of the pharynx muscles. Surprisingly, none of the tested CO2 avoidance mutants affected the rapid pumping inhibition response to elevated CO2 levels. A forward genetic screen identified that the hid-1-mediated pathway of dense core vesicle maturation regulates the pumping inhibition, probably through affecting neuropeptide secretion. Genetic studies and laser ablation experiments showed that the CO2 response of the pharyngeal muscle pumping is regulated by the BAG neurons, the same neurons that mediate CO2 avoidance.
二氧化碳(CO₂)是许多生物过程中的关键分子。对人类、小鼠、黑腹果蝇、秀丽隐杆线虫、单细胞生物和植物的研究揭示了由升高的CO₂水平激活的分子途径。然而,生物体用于感知和响应高CO₂水平的机制在很大程度上仍然未知。先前的研究表明,秀丽隐杆线虫通过涉及BAG、ASE和AFD神经元的机制,经由cGMP和钙信号通路快速避开升高的CO₂水平。在此,我们讨论我们最近的发现,即秀丽隐杆线虫暴露于高CO₂水平会导致咽肌收缩非常迅速地停止。令人惊讶的是,所测试的任何CO₂回避突变体均未影响对升高的CO₂水平的快速泵浦抑制反应。一项正向遗传筛选确定,hid-1介导的致密核心囊泡成熟途径可能通过影响神经肽分泌来调节泵浦抑制。遗传学研究和激光消融实验表明,咽肌泵浦的CO₂反应受BAG神经元调节,而BAG神经元也是介导CO₂回避的神经元。