A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release.
A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release.
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DOI：
10.1073/pnas.1804938115
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发表时间：
2018-08-07
影响因子：
11.1
通讯作者：
Beyder A
中科院分区：
文献类型：
--
作者：
Alcaino C;Knutson KR;Treichel AJ;Yildiz G;Strege PR;Linden DR;Li JH;Leiter AB;Szurszewski JH;Farrugia G;Beyder A
机械力对胃肠道的正常功能很重要。胃肠上皮中的肠嗜铬细胞被认为是一种特殊的感受器，可以将力量转化为5-羟色胺的释放，从这些细胞中释放的5-羟色胺对正常的胃肠道分泌和运动是重要的。这项研究的结果表明，一些肠嗜铬细胞确实是机械敏感的，它们使用机械敏感的Piezo2通道来产生离子电流，这对细胞内钙的增加、5-羟色胺的释放和上皮液的分泌至关重要。肠嗜铬细胞(EC)是肠上皮肠内分泌(EE)细胞中数量最多的细胞。EC细胞被认为是一种特殊的机械感觉细胞，能在上皮力的作用下释放5-羟色胺，从而调节肠液的分泌。然而，目前尚不清楚EE和EC细胞是否直接对机械敏感，如果是，其机械敏感的分子机制是什么。因此，EE和EC细胞在胃肠道机械生物学中的作用尚不清楚。Piezo2机械敏感离子通道是一些特殊的上皮机械传感器的重要组成部分，它们在鼠和人的EC细胞中都有表达。在这里，我们在多个小鼠模型中使用EC和EE细胞谱系追踪来表明Piezo2在小鼠EE和EC细胞的子集中表达，并且在超分辨显微镜下分布在5-羟色胺小泡附近。机械刺激分离的EE细胞子集导致快速内向离子电流，该电流可被Piezo2基因敲除和通道抑制剂减弱。在这些机械敏感的EE细胞中，作用力导致分离细胞和肠道器官内的EE细胞内依赖Piezo2的细胞内钙增加，以及EC细胞依赖Piezo2的机械敏感的5-羟色胺释放。肠道上皮细胞Piezo2的条件性基因敲除导致机械刺激的上皮细胞分泌显著减少。本研究表明，原代EE和EC细胞的一个亚群是机械敏感的，揭示了Piezo2是它们的主要机械转导分子，确定了它们机械转导和机械敏感的5-羟色胺释放的分子机制，并建立了Piezo2机械敏感离子通道在肠道生理调节中的作用。
Mechanical forces are important for normal gastrointestinal tract function. The enterochromaffin cells in the gastrointestinal epithelium have been proposed, but not previously shown, to be specialized sensors that convert forces into serotonin release, and serotonin released from these cells is important for normal gastrointestinal secretion and motility. The findings in this study show that some enterochromaffin cells are indeed mechanosensitive, and that they use mechanosensitive Piezo2 channels to generate an ionic current that is critical for the intracellular Ca2+ increase, serotonin release, and epithelial fluid secretion. Enterochromaffin (EC) cells constitute the largest population of intestinal epithelial enteroendocrine (EE) cells. EC cells are proposed to be specialized mechanosensory cells that release serotonin in response to epithelial forces, and thereby regulate intestinal fluid secretion. However, it is unknown whether EE and EC cells are directly mechanosensitive, and if so, what the molecular mechanism of their mechanosensitivity is. Consequently, the role of EE and EC cells in gastrointestinal mechanobiology is unclear. Piezo2 mechanosensitive ion channels are important for some specialized epithelial mechanosensors, and they are expressed in mouse and human EC cells. Here, we use EC and EE cell lineage tracing in multiple mouse models to show that Piezo2 is expressed in a subset of murine EE and EC cells, and it is distributed near serotonin vesicles by superresolution microscopy. Mechanical stimulation of a subset of isolated EE cells leads to a rapid inward ionic current, which is diminished by Piezo2 knockdown and channel inhibitors. In these mechanosensitive EE cells force leads to Piezo2-dependent intracellular Ca2+ increase in isolated cells as well as in EE cells within intestinal organoids, and Piezo2-dependent mechanosensitive serotonin release in EC cells. Conditional knockout of intestinal epithelial Piezo2 results in a significant decrease in mechanically stimulated epithelial secretion. This study shows that a subset of primary EE and EC cells is mechanosensitive, uncovers Piezo2 as their primary mechanotransducer, defines the molecular mechanism of their mechanotransduction and mechanosensitive serotonin release, and establishes the role of epithelial Piezo2 mechanosensitive ion channels in regulation of intestinal physiology.
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默克尔细胞转导并编码触觉刺激以驱动Aβ型冲动。
影响因子：
64.5
作者：
Ikeda R;Cha M;Ling J;Jia Z;Coyle D;Gu JG
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.1221400110
发表时间：
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影响因子：
11.1
作者：
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通讯作者：
Patapoutian, Ardem
影响因子：
64.5
作者：
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Julius D
DOI：
10.1152/ajpgi.00087.2011
发表时间：
2012-02-01
影响因子：
4.5
作者：
Chin, A.;Svejda, B.;Kidd, M.
通讯作者：
Kidd, M.