Howard Hughes Medical Institute andDepartment of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA 92037;
Howard Hughes Medical Institute andDepartment of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA 92037;Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121; and.
Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):10347-52. doi: 10.1073/pnas.1409233111. Epub 2014 Jun 23.
Mechanosensation is perhaps the last sensory modality not understood at the molecular level. Ion channels that sense mechanical force are postulated to play critical roles in a variety of biological processes including sensing touch/pain (somatosensation), sound (hearing), and shear stress (cardiovascular physiology); however, the identity of these ion channels has remained elusive. We previously identified Piezo1 and Piezo2 as mechanically activated cation channels that are expressed in many mechanosensitive cell types. Here, we show that Piezo1 is expressed in endothelial cells of developing blood vessels in mice. Piezo1-deficient embryos die at midgestation with defects in vascular remodeling, a process critically influenced by blood flow. We demonstrate that Piezo1 is activated by shear stress, the major type of mechanical force experienced by endothelial cells in response to blood flow. Furthermore, loss of Piezo1 in endothelial cells leads to deficits in stress fiber and cellular orientation in response to shear stress, linking Piezo1 mechanotransduction to regulation of cell morphology. These findings highlight an essential role of mammalian Piezo1 in vascular development during embryonic development.
机械感觉或许是分子水平上尚未被理解的最后一种感觉模式。人们推测，能够感知机械力的离子通道在多种生物过程中发挥着关键作用，包括触觉/疼痛（躯体感觉）、声音（听觉）和切应力（心血管生理学）；然而，这些离子通道的身份仍然难以捉摸。我们之前鉴定出 Piezo1 和 Piezo2 是机械激活的阳离子通道，在许多机械敏感细胞类型中表达。在这里，我们表明 Piezo1 在发育中小鼠血管中的内皮细胞中表达。Piezo1 缺陷型胚胎在妊娠中期死亡，血管重塑缺陷，这一过程受到血流的严重影响。我们证明 Piezo1 被切应力激活，这是内皮细胞在血流作用下所经历的主要类型的机械力。此外，内皮细胞中 Piezo1 的缺失导致细胞在切应力下的应力纤维和细胞取向缺陷，将 Piezo1 的机械转导与细胞形态的调节联系起来。这些发现强调了哺乳动物 Piezo1 在胚胎发育过程中血管发育中的重要作用。
