College of Life Science and Technology, Key Laboratory of Molecular Biophysics of MOE, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China; Life Sciences Institute, Ann Arbor, MI, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Life Sciences Institute, Ann Arbor, MI, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Curr Biol. 2024 Nov 18;34(22):5382-5391.e3. doi: 10.1016/j.cub.2024.09.075. Epub 2024 Oct 28.
Shear stress sensing represents a vital mode of mechanosensation. Previous efforts have mainly focused on characterizing how various cell types-for example, vascular endothelial cells-sense shear stress arising from fluid flow within the animal body. How animals sense shear stress derived from their external environment, however, is not well understood. Here, using C. elegans as a model, we show that external fluid flow triggers behavioral responses in C. elegans, facilitating their navigation of the environment during swimming. Such behavioral responses primarily result from shear stress generated by fluid flow. The sensory neurons AWC, ASH, and ASER are the major shear stress-sensitive neurons, among which AWC shows the most robust response to shear stress and is required for shear stress-induced behavior. Mechanistically, shear stress signals are transduced by G protein signaling in AWC, with cGMP as the second messenger, culminating in the opening of cGMP-sensitive cyclic nucleotide-gated (CNG) channels and neuronal excitation. These studies demonstrate that C. elegans senses and responds to shear stress and characterize the underlying neural and molecular mechanisms. Our work helps establish C. elegans as a genetic model for studying shear stress sensing.
切应力感应代表了一种重要的机械感觉模式。以前的研究主要集中在描述各种细胞类型(例如血管内皮细胞)如何感知来自体内流体流动的切应力。然而,动物如何感知来自外部环境的切应力还不是很清楚。在这里,我们使用秀丽隐杆线虫作为模型,表明外部流体流动会引发线虫的行为反应,帮助它们在游泳时在环境中导航。这种行为反应主要是由流体流动产生的切应力引起的。感觉神经元 AWC、ASH 和 ASER 是主要的切应力敏感神经元,其中 AWC 对切应力的反应最为强烈,并且是切应力诱导行为所必需的。从机制上讲,切应力信号通过 AWC 中的 G 蛋白信号转导,以 cGMP 作为第二信使,最终导致 cGMP 敏感的环核苷酸门控 (CNG) 通道的开放和神经元兴奋。这些研究表明,秀丽隐杆线虫能够感知和响应切应力,并描述了潜在的神经和分子机制。我们的工作有助于将秀丽隐杆线虫确立为研究切应力感应的遗传模型。