Thermosensory and nonthermosensory isoforms of Drosophila melanogaster TRPA1 reveal heat-sensor domains of a thermoTRP Channel.

Thermosensory and nonthermosensory isoforms of Drosophila melanogaster TRPA1 reveal heat-sensor domains of a thermoTRP Channel.
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DOI:
10.1016/j.celrep.2011.11.002
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发表时间:
2012-01-26
期刊:
影响因子:
8.8
通讯作者:
Tracey WD
Tracey WD
中科院分区:
生物学1区
文献类型:
--
作者:
Zhong L;Bellemer A;Yan H;Ken H;Jessica R;Hwang RY;Pitt GS;Tracey WD

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专门的躯体感觉神经元检测从舒适的凉爽或温暖到灼热和疼痛(伤害感受)的温度。由热敏神经元感知的精确温度范围由瞬时受体电位(TRP)家族的离子通道的组织特异性表达决定。我们在这里表明,在果蝇中,TRPA 1是感受伤害性热所必需的。我们确定了两个新的蛋白质亚型dTRPA 1命名dTRPA 1-C和dTRPA 1-D,解释了这一要求。dTRPA 1-C/D报告基因仅在伤害感受器中表达,并且当恢复到突变伤害感受器时,dTRPA 1-C挽救了热伤害感受表型。然而,令人惊讶的是,我们发现dTRPA 1-C不是直接的热传感器。选择性剪接产生至少四种dTRPA 1亚型。我们对这些亚型的分析揭示了一个37个氨基酸的细胞内区域(由单个外显子编码),这对dTRPA 1温度反应至关重要。这些氨基酸的鉴定打开了一扇大门,以生物物理学的理解的分子温度传感器。
Specialized somatosensory neurons detect temperatures ranging from pleasantly cool or warm to burning hot and painful (nociceptive). The precise temperature ranges sensed by thermally sensitive neurons is determined by tissue specific expression of ion channels of the Transient Receptor Potential (TRP) family. We show here, that in Drosophila, TRPA1 is required for sensing of nociceptive heat. We identify two new protein isoforms of dTRPA1named dTRPA1-C and dTRPA1-D that explain this requirement. A dTRPA1-C/D reporter was exclusively expressed in nociceptors and dTRPA1-C rescued thermal nociception phenotypes when restored to mutant nociceptors. However, surprisingly, we find that dTRPA1-C is not a direct heat sensor. Alternative splicing generates at least four isoforms of dTRPA1. Our analysis of these isoforms reveals a 37 amino acid intracellular region (encoded by a single exon) that is critical for dTRPA1 temperature responses. The identification of these amino acids opens the door to a biophysical understanding of a molecular thermosensor.
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