Ridone Pietro, Vassalli Massimo, Martinac Boris
Mechanosensory Biophysics Laboratory, Victor Chang Cardiac Research Institute, 405 Liverpool St, Darlinghurst, NSW, 2010, Australia.
School of Biotechnology and Biomolecular Science, University of New South Wales, Kensington, NSW, 2052, Australia.
Biophys Rev. 2019 Oct;11(5):795-805. doi: 10.1007/s12551-019-00584-5. Epub 2019 Sep 7.
Mechanosensitive (MS) ion channels are integral membrane proteins which play a crucial role in fast signaling during mechanosensory transduction processes in living cells. They are ubiquitous and old in the evolutionary sense, given their presence in cells from all three kingdoms of life found on Earth, including bacterial, archaeal, and eukaryotic organisms. As molecular transducers of mechanical force, MS channels are activated by mechanical stimuli exerted on cellular membranes, upon which they rapidly and efficiently convert these stimuli into electrical, osmotic, and/or chemical intracellular signals. Most of what we know about the gating mechanisms of MS channels comes from the work carried out on bacterial channels. However, recent progress resulting from identification and structural information of eukaryotic K2P-type TREK and TRAAK as well as Piezo1 and Piezo2 MS channels has greatly contributed to our understanding of the common biophysical principles underlying the gating mechanism and evolutionary origins of these fascinating membrane proteins. Using Piezo1 channels as an example, we briefly describe in this review what we have learned about their biophysics, physiological functions, and potential roles in "mechanopathologies."
机械敏感(MS)离子通道是整合膜蛋白,在活细胞的机械感觉转导过程中的快速信号传导中起关键作用。从进化的角度来看,它们无处不在且存在已久,因为在地球上发现的生命的所有三个界的细胞中都有它们的存在,包括细菌、古细菌和真核生物。作为机械力的分子转换器,MS通道被施加在细胞膜上的机械刺激激活,在此之后它们迅速而有效地将这些刺激转化为电、渗透和/或化学细胞内信号。我们对MS通道门控机制的了解大多来自对细菌通道的研究。然而,真核生物K2P型TREK和TRAAK以及Piezo1和Piezo2 MS通道的鉴定和结构信息所带来的最新进展,极大地促进了我们对这些迷人膜蛋白门控机制和进化起源背后共同生物物理原理的理解。以Piezo1通道为例,我们在本综述中简要描述了我们对其生物物理学、生理功能以及在“机械病理学”中的潜在作用的了解。