在这周Nature上发表的两篇里程碑样文章中，斯克里普斯研究所的科学家报道他们已鉴定了检测“疼痛接触”的一类蛋白质。
已知我们皮肤里的感觉神经使用它们外层膜里的专门"离子通道"蛋白来检测压力、疼痛、热、冷和其他他刺激。但是他们也只是刚开始鉴定和特征化参与每一种感觉传导通路的专门蛋白。新工作提供了证据，称为压力蛋白的感觉神经蛋白家族是疼痛接触感觉必不可少的离子通道蛋白。
新研究中的实验在哺乳动物感觉神经系统的模型系统果蝇中开展，压力蛋白也在果蝇中表达，以及耳、肾、心和其他组织内的某些类型细胞中表达。将来的研究将集中于压力蛋白在传感声音、血压及压和/或拉伸细胞膜的相关刺激中的作用。
两篇文章都在线发表于2月19日的Nature上。（生物谷bioon.com）
doi:10.1038/nature10801
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The role of Drosophila Piezo in mechanical nociception
Sung Eun Kim, Bertrand Coste, Abhishek Chadha, Boaz Cook, Ardem Patapoutian
ABSTRACT Transduction of mechanical stimuli by receptor cells is essential for senses such as hearing, touch and pain. Ion channels have a role in neuronal mechanotransduction in invertebrates; however, functional conservation of these ion channels in mammalian mechanotransduction is not observed. For example, no mechanoreceptor potential C (NOMPC), a member of transient receptor potential (TRP) ion channel family, acts as a mechanotransducer in Drosophila melanogaster and Caenorhabditis elegan; however, it has no orthologues in mammals. Degenerin/epithelial sodium channel (DEG/ENaC) family members are mechanotransducers in C. elegans and potentially in D. melanogaster; however, a direct role of its mammalian homologues in sensing mechanical force has not been shown. Recently, Piezo1 (also known as Fam38a) and Piezo2 (also known as Fam38b) were identified as components of mechanically activated channels in mammals. The Piezo family are evolutionarily conserved transmembrane proteins. It is unknown whether they function in mechanical sensing in vivo and, if they do, which mechanosensory modalities they mediate. Here we study the physiological role of the single Piezo member in D. melanogaster (Dmpiezo; also known as CG8486). Dmpiezo expression in human cells induces mechanically activated currents, similar to its mammalian counterparts. Behavioural responses to noxious mechanical stimuli were severely reduced in Dmpiezo knockout larvae, whereas responses to another noxious stimulus or touch were not affected. Knocking down Dmpiezo in sensory neurons that mediate nociception and express the DEG/ENaC ion channel pickpocket (ppk) was sufficient to impair responses to noxious mechanical stimuli. Furthermore, expression of Dmpiezo in these same neurons rescued the phenotype of the constitutive Dmpiezo knockout larvae. Accordingly, electrophysiological recordings from ppk-positive neurons revealed a Dmpiezo-dependent, mechanically activated current. Finally, we found that Dmpiezo and ppk function in parallel pathways in ppk-positive cells, and that mechanical nociception is abolished in the absence of both channels. These data demonstrate the physiological relevance of the Piezo family in mechanotransduction in vivo, supporting a role of Piezo proteins in mechanosensory nociception.
doi:10.1038/nature10812
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Piezo proteins are pore-forming subunits of mechanically activated channels
Bertrand Coste, Bailong Xiao, Jose S. Santos, Ruhma Syeda, J?rg Grandl, Kathryn S. Spencer, Sung Eun Kim, Manuela Schmidt, Jayanti Mathur, Adrienne E. Dubin, Mauricio Montal, Ardem Patapoutian
ABSTRACT Mechanotransduction has an important role in physiology. Biological processes including sensing touch and sound waves require as-yet-unidentified cation channels that detect pressure. Mouse Piezo1 (MmPiezo1) and MmPiezo2 (also called Fam38a and Fam38b, respectively) induce mechanically activated cationic currents in cells; however, it is unknown whether Piezo proteins are pore-forming ion channels or modulate ion channels. Here we show that Drosophila melanogaster Piezo (DmPiezo, also called CG8486) also induces mechanically activated currents in cells, but through channels with remarkably distinct pore properties including sensitivity to the pore blocker ruthenium red and single channel conductances. MmPiezo1 assembles as a ~1.2-million-dalton homo-oligomer, with no evidence of other proteins in this complex. Purified MmPiezo1 reconstituted into asymmetric lipid bilayers and liposomes forms ruthenium-red-sensitive ion channels. These data demonstrate that Piezo proteins are an evolutionarily conserved ion channel family involved in mechanotransduction.
