Sharabi Kfir, Charar Chayki, Friedman Nurit, Mizrahi Inbar, Zaslaver Alon, Sznajder Jacob I, Gruenbaum Yosef
Department of Genetics, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
PLoS Genet. 2014 Aug 7;10(8):e1004529. doi: 10.1371/journal.pgen.1004529. eCollection 2014 Aug.
Carbon dioxide (CO2) is a key molecule in many biological processes; however, mechanisms by which organisms sense and respond to high CO2 levels remain largely unknown. Here we report that acute CO2 exposure leads to a rapid cessation in the contraction of the pharynx muscles in Caenorhabditis elegans. To uncover the molecular mechanisms underlying this response, we performed a forward genetic screen and found that hid-1, a key component in neuropeptide signaling, regulates this inhibition in muscle contraction. Surprisingly, we found that this hid-1-mediated pathway is independent of any previously known pathways controlling CO2 avoidance and oxygen sensing. In addition, animals with mutations in unc-31 and egl-21 (neuropeptide secretion and maturation components) show impaired inhibition of muscle contraction following acute exposure to high CO2 levels, in further support of our findings. Interestingly, the observed response in the pharynx muscle requires the BAG neurons, which also mediate CO2 avoidance. This novel hid-1-mediated pathway sheds new light on the physiological effects of high CO2 levels on animals at the organism-wide level.
二氧化碳（CO₂）是许多生物过程中的关键分子；然而，生物体感知和响应高二氧化碳水平的机制在很大程度上仍不为人知。在此，我们报告急性二氧化碳暴露会导致秀丽隐杆线虫咽部肌肉收缩迅速停止。为了揭示这种反应背后的分子机制，我们进行了正向遗传学筛选，发现hid - 1（神经肽信号传导的关键成分）调节肌肉收缩的这种抑制作用。令人惊讶的是，我们发现这种hid - 1介导的途径独立于任何先前已知的控制二氧化碳回避和氧气感知的途径。此外，unc - 31和egl - 21（神经肽分泌和成熟成分）发生突变的动物在急性暴露于高二氧化碳水平后，肌肉收缩抑制受损，这进一步支持了我们的发现。有趣的是，咽部肌肉中观察到的反应需要BAG神经元，而BAG神经元也介导二氧化碳回避。这种新的hid - 1介导的途径在全生物体水平上为高二氧化碳水平对动物的生理影响提供了新的见解。
