Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, United States of America.
PLoS One. 2012;7(1):e30090. doi: 10.1371/journal.pone.0030090. Epub 2012 Jan 25.
The Drosophila TRPA channel Painless is required for the function of polymodal nociceptors which detect noxious heat and noxious mechanical stimuli. These functions of Painless are reminiscent of mammalian TRPA channels that have also been implicated in thermal and mechanical nociception. A popular hypothesis to explain the mechanosensory functions of certain TRP channels proposes that a string of ankyrin repeats at the amino termini of these channels acts as an intracellular spring that senses force. Here, we describe the identification of two previously unknown Painless protein isoforms which have fewer ankyrin repeats than the canonical Painless protein. We show that one of these Painless isoforms, that essentially lacks ankyrin repeats, is sufficient to rescue mechanical nociception phenotypes of painless mutant animals but does not rescue thermal nociception phenotypes. In contrast, canonical Painless, which contains Ankyrin repeats, is sufficient to largely rescue thermal nociception but is not capable of rescuing mechanical nociception. Thus, we propose that in the case of Painless, ankryin repeats are important for thermal nociception but not for mechanical nociception.
果蝇 TRPA 通道 Painless 对于检测有害热和有害机械刺激的多模态伤害感受器的功能是必需的。Painless 的这些功能让人联想到也与热和机械伤害感受有关的哺乳动物 TRPA 通道。一个流行的假设是解释某些 TRP 通道的机械感觉功能，该假设提出这些通道氨基末端的一连串锚蛋白重复序列充当感应力的细胞内弹簧。在这里，我们描述了两个先前未知的 Painless 蛋白同工型的鉴定，它们的锚蛋白重复序列比典型的 Painless 蛋白少。我们表明，这些 Painless 同工型之一，本质上缺乏锚蛋白重复序列，足以挽救 painful 突变体动物的机械伤害感受表型，但不能挽救热伤害感受表型。相比之下，含有锚蛋白重复序列的典型 Painless 足以在很大程度上挽救热伤害感受，但不能挽救机械伤害感受。因此，我们提出在 Painless 的情况下，锚蛋白重复序列对于热伤害感受很重要，但对于机械伤害感受不重要。
