National Center for Behavioral Genomics and Volen Center for Complex Systems, Department of Biology, Brandeis University, Waltham, Massachusetts 02454, USA.
Nature. 2011 Dec 4;481(7379):76-80. doi: 10.1038/nature10715.
Discriminating among sensory stimuli is critical for animal survival. This discrimination is particularly essential when evaluating whether a stimulus is noxious or innocuous. From insects to humans, transient receptor potential (TRP) channels are key transducers of thermal, chemical and other sensory cues. Many TRPs are multimodal receptors that respond to diverse stimuli, but how animals distinguish sensory inputs activating the same TRP is largely unknown. Here we determine how stimuli activating Drosophila TRPA1 are discriminated. Although Drosophila TRPA1 responds to both noxious chemicals and innocuous warming, we find that TRPA1-expressing chemosensory neurons respond to chemicals but not warmth, a specificity conferred by a chemosensory-specific TRPA1 isoform with reduced thermosensitivity compared to the previously described isoform. At the molecular level, this reduction results from a unique region that robustly reduces the channel's thermosensitivity. Cell-type segregation of TRPA1 activity is critical: when the thermosensory isoform is expressed in chemosensors, flies respond to innocuous warming with regurgitation, a nocifensive response. TRPA1 isoform diversity is conserved in malaria mosquitoes, indicating that similar mechanisms may allow discrimination of host-derived warmth--an attractant--from chemical repellents. These findings indicate that reducing thermosensitivity can be critical for TRP channel functional diversification, facilitating their use in contexts in which thermal sensitivity can be maladaptive.
区分感觉刺激对于动物的生存至关重要。这种区分在评估刺激是有害还是无害时尤为重要。从昆虫到人类,瞬时受体电位 (TRP) 通道是热、化学和其他感觉线索的关键转导器。许多 TRP 是多模态受体,可以对多种刺激做出反应,但动物如何区分激活相同 TRP 的感觉输入在很大程度上是未知的。在这里,我们确定了激活果蝇 TRPA1 的刺激是如何被区分的。尽管果蝇 TRPA1 对有害化学物质和无害的升温都有反应,但我们发现表达 TRPA1 的化学感觉神经元对化学物质有反应,但对温度没有反应,这种特异性是由一种化学感觉特异性的 TRPA1 同工型赋予的,与之前描述的同工型相比,其热敏感性降低。在分子水平上,这种减少是由于一个独特的区域,该区域强烈降低了通道的热敏感性。TRPA1 活性的细胞类型分离是至关重要的:当热敏同工型在化学感受器中表达时,苍蝇会对无害的升温做出呕吐反应,这是一种防御性反应。TRPA1 同工型多样性在疟疾蚊子中是保守的,这表明类似的机制可能允许区分宿主来源的温暖——一种吸引力——与化学驱避剂。这些发现表明,降低热敏感性对于 TRP 通道功能多样化可能是至关重要的,这有助于它们在热敏感性可能不适应的情况下使用。