Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell Rep. 2014 Jan 16;6(1):70-80. doi: 10.1016/j.celrep.2013.12.012. Epub 2014 Jan 2.
Mechanoelectrical transduction (MeT) channels embedded in neuronal cell membranes are essential for touch and proprioception. Little is understood about the interplay between native MeT channels and membrane phospholipids, in part because few techniques are available for altering plasma membrane composition in vivo. Here, we leverage genetic dissection, chemical complementation, and optogenetics to establish that arachidonic acid (AA), an omega-6 polyunsaturated fatty acid, enhances touch sensation and mechanoelectrical transduction activity while incorporated into membrane phospholipids in C. elegans touch receptor neurons (TRNs). Because dynamic force spectroscopy reveals that AA modulates the mechanical properties of TRN plasma membranes, we propose that this polyunsaturated fatty acid (PUFA) is needed for MeT channel activity. These findings establish that polyunsaturated phospholipids are crucial determinants of both the biochemistry and mechanics of mechanoreceptor neurons and reinforce the idea that sensory mechanotransduction in animals relies on a cellular machine composed of both proteins and membrane lipids.
机械电转换(MeT)通道嵌入神经元细胞膜中,对于触摸和本体感觉至关重要。目前对于天然 MeT 通道与膜磷脂之间的相互作用知之甚少,部分原因是很少有技术可用于在体内改变质膜组成。在这里,我们利用遗传解析、化学互补和光遗传学来确定花生四烯酸(AA),一种ω-6 多不饱和脂肪酸,在整合到秀丽隐杆线虫触觉受体神经元(TRN)的膜磷脂中时,可增强触觉感知和机械电转换活性。由于动态力谱表明 AA 调节 TRN 质膜的机械性能,我们提出这种多不饱和脂肪酸(PUFA)是 MeT 通道活性所必需的。这些发现确立了多不饱和磷脂是机械感受器神经元的生物化学和力学的关键决定因素,并强化了这样一种观点,即动物的感觉机械转导依赖于由蛋白质和膜脂组成的细胞机器。