Kuck Lennart, Kaestner Lars, Egée Stéphane, Lew Virgilio L, Simmonds Michael J
Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia.
Theoretical Medicine and Biosciences, Medical Faculty, Saarland University, Homburg, Germany.
Channels (Austin). 2025 Dec;19(1):2556105. doi: 10.1080/19336950.2025.2556105. Epub 2025 Sep 10.
The hallmarks of mechanosensitive ion channels have been observed for half a century in various cell lines, although their mechanisms and molecular identities remained unknown until recently. Identification of the bona fide mammalian mechanosensory Piezo channels resulted in an explosion of research exploring the translation of mechanical cues into biochemical signals and dynamic cell morphology responses. One of the Piezo isoforms - Piezo1 - is integral in the erythrocyte (red blood cell; RBC) membrane. The exceptional flexibility of RBCs and the absence of intracellular organelles provides a unique mechanical and biochemical environment dictating specific Piezo1-functionality. The Piezo1-endowed capacity of RBCs to sense the mechanical forces acting upon them during their continuous traversal of the circulatory system has solidified a brewing step-change in our fundamental understanding of RBC biology in health and disease; that is, RBCs are not biologically inert but rather capable of complex dynamic cellular signaling. Although several lines of investigation have unearthed various regulatory mechanisms of signaling pathway activation by RBC-Piezo1, these independent studies have not yet been synthesized into a cohesive picture. The aim of the present review is to thus summarize the progress in elucidating how Piezo1 functions in the unique cellular environment of RBCs, challenge classical views of this enucleated cell, and provoke developments for future work.
半个世纪以来，人们在各种细胞系中都观察到了机械敏感离子通道的特征，尽管直到最近其机制和分子身份仍不为人知。真正的哺乳动物机械感觉Piezo通道的鉴定引发了一系列研究热潮，这些研究探索了如何将机械信号转化为生化信号以及动态细胞形态反应。Piezo亚型之一——Piezo1——是红细胞（RBC）膜的组成部分。红细胞具有非凡的柔韧性且缺乏细胞内细胞器，这提供了一个独特的机械和生化环境，决定了Piezo1的特定功能。在红细胞持续穿越循环系统的过程中，Piezo1赋予其感知作用于自身的机械力的能力，这巩固了我们对健康和疾病状态下红细胞生物学的基本理解中正在酝酿的一个重大转变；也就是说，红细胞并非生物学上的惰性细胞，而是能够进行复杂的动态细胞信号传导。尽管多项研究揭示了红细胞Piezo1激活信号通路的各种调控机制，但这些独立的研究尚未整合形成一个连贯的图景。因此，本综述的目的是总结在阐明Piezo1在红细胞独特细胞环境中的功能方面所取得的进展，挑战对这种无核细胞的传统观点，并推动未来研究的发展。
