在這周Nature上發(fā)表的兩篇里程碑樣文章中,，斯克里普斯研究所的科學(xué)家報道他們已鑒定了檢測“疼痛接觸”的一類蛋白質(zhì),。

已知我們皮膚里的感覺神經(jīng)使用它們外層膜里的專門"離子通道"蛋白來檢測壓力,、疼痛、熱,、冷和其他他刺激,。但是他們也只是剛開始鑒定和特征化參與每一種感覺傳導(dǎo)通路的專門蛋白。新工作提供了證據(jù),，稱為壓力蛋白的感覺神經(jīng)蛋白家族是疼痛接觸感覺必不可少的離子通道蛋白,。

新研究中的實驗在哺乳動物感覺神經(jīng)系統(tǒng)的模型系統(tǒng)果蠅中開展，壓力蛋白也在果蠅中表達(dá),，以及耳,、腎、心和其他組織內(nèi)的某些類型細(xì)胞中表達(dá),。將來的研究將集中于壓力蛋白在傳感聲音,、血壓及壓和/或拉伸細(xì)胞膜的相關(guān)刺激中的作用。

兩篇文章都在線發(fā)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.