the ankyrin repeat domain of the trpa protein painless is important for thermal nociception but not mechanical nociception锚蛋白重复域trpa蛋白质的无痛对热伤害感受很重要但不是机械痛觉过敏.pdf

The Ankyrin Repeat Domain of the TRPA Protein Painless Is Important for Thermal Nociception but Not Mechanical Nociception 3 1 1,2,3 Richard Y. Hwang , Nancy A. Stearns , W. Daniel Tracey * 1 Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, United States of America, 2 Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, United States of America, 3 Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, United States of America Abstract 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. Cit