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mechanosensitive channel

Rose Z Hill, Benjamin U Hoffman, Takeshi Morita, Stephanie M Campos, Ellen A Lumpkin, Rachel B Brem, Diana M Bautista
Somatosensory neurons mediate responses to diverse mechanical stimuli, from innocuous touch to noxious pain. While recent studies have identified distinct populations of A mechanonociceptors (AMs) that are required for mechanical pain, the molecular underpinnings of mechanonociception remain unknown. Here, we show that the bioactive lipid sphingosine 1-phosphate (S1P) and S1P Receptor 3 (S1PR3) are critical regulators of acute mechanonociception. Genetic or pharmacological ablation of S1PR3, or blockade of S1P production, significantly impaired the behavioral response to noxious mechanical stimuli, with no effect on responses to innocuous touch or thermal stimuli...
March 21, 2018: ELife
Holger Fehlauer, Adam L Nekimken, Anna A Kim, Beth L Pruitt, Miriam B Goodman, Michael Krieg
One central goal of mechanobiology is to understand the reciprocal effect of mechanical stress on proteins and cells. Despite its importance, the influence of mechanical stress on cellular function is still poorly understood. In part, this knowledge gap exists because few tools enable simultaneous deformation of tissue and cells, imaging of cellular activity in live animals, and efficient restriction of motility in otherwise highly mobile model organisms, such as the nematode Caenorhabditis elegans. The small size of C...
February 19, 2018: Journal of Visualized Experiments: JoVE
Mirko Moroni, M Rocio Servin-Vences, Raluca Fleischer, Oscar Sánchez-Carranza, Gary R Lewin
Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage-gated mode. Mutations that cause human diseases, such as xerocytosis, profoundly shift voltage sensitivity of PIEZO1 channels toward the resting membrane potential and strongly promote voltage gating. Voltage modulation may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation...
March 15, 2018: Nature Communications
Martin Loynaz Prieto, Kamyar Firouzi, Butrus T Khuri-Yakub, Merritt Maduke
Ultrasound (US) can modulate the electrical activity of the excitable tissues, but the mechanisms underlying this effect are not understood at the molecular level or in terms of the physical modality through which US exerts its effects. Here, we report an experimental system that allows for stable patch-clamp recording in the presence of US at 43 MHz, a frequency known to stimulate neural activity. We describe the effects of US on two ion channels proposed to be involved in the response of excitable cells to US: the mechanosensitive Piezo1 channel and the voltage-gated sodium channel NaV 1...
March 7, 2018: Ultrasound in Medicine & Biology
Elizabeth L Evans, Kevin Cuthbertson, Naima Endesh, Baptiste Rode, Nicola M Blythe, Adam J Hyman, Sally J Hall, Hannah J Gaunt, Melanie J Ludlow, Richard Foster, David J Beech
BACKGROUND AND PURPOSE: The mechanosensitive Piezo1 channel has important roles in vascular physiology and disease. Yoda1 is a small-molecule agonist but the pharmacology of these channels is otherwise limited. EXPERIMENTAL APPROACH: Yoda1 analogues were generated by synthetic chemistry. Intracellular Ca2+ and Tl+ measurements were made in HEK 293 or CHO cell lines overexpressing channel subunits and in human umbilical vein endothelial cells (HUVECs) which natively express Piezo1...
March 2, 2018: British Journal of Pharmacology
Michele A Corrigan, Gillian P Johnson, Elena Stavenschi, Mathieu Riffault, Marie-Noelle Labour, David A Hoey
Skeletal homeostasis requires the continued replenishment of the bone forming osteoblast from a mesenchymal stem cell (MSC) population, a process that has been shown to be mechanically regulated. However, the mechanisms by which a biophysical stimulus can induce a change in biochemical signaling, mechanotransduction, is poorly understood. As a precursor to loading-induced bone formation, deciphering the molecular mechanisms of MSC osteogenesis is a critical step in developing novel anabolic therapies. Therefore, in this study we characterize the expression of the mechanosensitive calcium channel Transient Receptor Potential subfamily V member 4 (TRPV4) in MSCs and demonstrate that TRPV4 localizes to areas of high strain, specifically the primary cilium...
February 28, 2018: Scientific Reports
J Won, H Vang, J H Kim, P R Lee, Y Kang, S B Oh
Odontoblasts, with their strategic arrangement along the outermost compartment of the dentin-pulp complex, have been suggested to have sensory function. In addition to their primary role in dentin formation, growing evidence shows that odontoblasts are capable of sensing mechanical stimulation. Previously, we found that most odontoblasts express TRPM7, the nonselective mechanosensitive ion channel reported to be critical in Mg2+ homeostasis and dentin mineralization. In line with this finding, we sought to elucidate the functional expression of TRPM7 in odontoblasts by pharmacological approaches and mechanical stimulation...
February 1, 2018: Journal of Dental Research
Qiancheng Zhao, Heng Zhou, Shaopeng Chi, Yanfeng Wang, Jianhua Wang, Jie Geng, Kun Wu, Wenhao Liu, Tingxin Zhang, Meng-Qiu Dong, Jiawei Wang, Xueming Li, Bailong Xiao
The mechanosensitive Piezo channels function as key eukaryotic mechanotransducers. However, their structures and mechanogating mechanisms remain unknown. Here we determine the three-bladed, propeller-like electron cryo-microscopy structure of mouse Piezo1 and functionally reveal its mechanotransduction components. Despite the lack of sequence repetition, we identify nine repetitive units consisting of four transmembrane helices each-which we term transmembrane helical units (THUs)-which assemble into a highly curved blade-like structure...
February 22, 2018: Nature
Naoki Aizawa, Yoshikazu Fujimori, Jun-Ichi Kobayashi, Osamu Nakanishi, Hideaki Hirasawa, Haruki Kume, Yukio Homma, Yasuhiko Igawa
AIMS: Transient receptor potential melastatin 8 (TRPM8) is proposed to be a promising therapeutic target for hypersensitive bladder disorders. We examined the effects of KPR-2579, a novel selective TRPM8 antagonist, on body temperature and on mechanosensitive bladder single-unit afferent activities (SAAs) provoked by intravesical acetic acid (AA) instillation in rats. METHODS: Female Sprague-Dawley rats were used. Effects of cumulative intravenous (i.v.) administrations of KPR-2579 (0...
February 21, 2018: Neurourology and Urodynamics
Tim Rasmussen, Akiko Rasmussen
Mechanosensitive (MS) channels protect bacteria against hypo-osmotic shock and fulfil additional functions. Hypo-osmotic shock leads to high turgor pressure that can cause cell rupture and death. MS channels open under these conditions and release unspecifically solutes and consequently the turgor pressure. They can recognise the raised pressure via the increased tension in the cell membrane. Currently, a better understanding how MS channels can sense tension on molecular level is developing because the interaction of the lipid bilayer with the channel is being investigated in detail...
2018: Sub-cellular Biochemistry
Jan Kubanek, Poojan Shukla, Alakananda Das, Stephen A Baccus, Miriam B Goodman
Focused ultrasound has been shown to stimulate excitable cells, but the biophysical mechanisms behind this phenomenon remain poorly understood. To provide additional insight, we devised a behavioralgenetic assay applied to the well-characterized nervous system of C. elegans nematodes. We found that pulsed ultrasound elicits robust reversal behavior in wild-type animals in a pressure-, duration-, and pulse protocol- dependent manner. Responses were preserved in mutants unable to sense thermal fluctuations and absent in mutants lacking neurons required for mechanosensation...
February 20, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Yoshie Narui, Marcos Sotomayor
Human hearing relies upon the tip-to-tip interaction of two non-classical cadherins, protocadherin-15 (PCDH15) and cadherin-23 (CDH23). Together, these proteins form a filament called the tip link that connects neighboring stereocilia of mechanosensitive hair cells. As sound waves enter the cochlea, the stereocilia deflect and tension is applied to the tip link opening nearby transduction channels. Disruption of the tip link by loud sound or calcium chelators eliminates transduction currents and illustrates that tip-link integrity is critical for mechanosensing...
February 14, 2018: Biochemistry
Carlos Pardo-Pastor, Fanny Rubio-Moscardo, Marina Vogel-González, Selma A Serra, Alexandros Afthinos, Sanela Mrkonjic, Olivier Destaing, Juan F Abenza, José M Fernández-Fernández, Xavier Trepat, Corinne Albiges-Rizo, Konstantinos Konstantopoulos, Miguel A Valverde
Actin polymerization and assembly into stress fibers (SFs) is central to many cellular processes. However, how SFs form in response to the mechanical interaction of cells with their environment is not fully understood. Here we have identified Piezo2 mechanosensitive cationic channel as a transducer of environmental physical cues into mechanobiological responses. Piezo2 is needed by brain metastatic cells from breast cancer (MDA-MB-231-BrM2) to probe their physical environment as they anchor and pull on their surroundings or when confronted with confined migration through narrow pores...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Nathaniel G Dela Paz, John A Frangos
Piezo1 is a mechanosensitive cation channel that is activated by shear stress in endothelial cells (ECs). It has been shown to mediate shear-induced EC responses, including increased calcium influx, and vascular functions, such as vascular tone and blood pressure. Yoda1, a selective Piezo1 activator, has been shown to mimic shear-induced responses in ECs. Since shear-induced calcium influx causes Akt and ERK1/2 activation in ECs, we examined the effects of Yoda1 and the role of Piezo1 on their activation. Here, we show that Yoda1 robustly activates Akt and ERK1/2 in ECs...
February 8, 2018: Biochemical and Biophysical Research Communications
Jérémie Barral, Frank Jülicher, Pascal Martin
Hair cells of the inner ear can power spontaneous oscillations of their mechanosensory hair bundle, resulting in amplification of weak inputs near the characteristic frequency of oscillation. Recently, dynamic force measurements have revealed that delayed gating of the mechanosensitive ion channels responsible for mechanoelectrical transduction produces a friction force on the hair bundle. The significance of this intrinsic source of dissipation for the dynamical process underlying active hair-bundle motility has remained elusive...
January 23, 2018: Biophysical Journal
Alexander Klesen, Dorothee Jakob, Ramona Emig, Peter Kohl, Ursula Ravens, Rémi Peyronnet
Fibrotic areas in cardiac muscle-be it in ventricular or atrial tissue-are considered as obstacles for conduction of the excitatory wave and can therefore facilitate re-entry, which may contribute to the sustenance of cardiac arrhythmias. Persistence of one of the most frequent arrhythmias, atrial fibrillation (AF), is accompanied by enhanced atrial fibrosis. Any kind of myocardial perturbation, whether via mechanical stress or ischemic damage, inflammation, or irregular and high-frequency electrical activity, activates fibroblasts...
February 1, 2018: Herzschrittmachertherapie & Elektrophysiologie
Rosa Morra, Francesco Del Carratore, Howbeer Muhamadali, Luminita Gabriela Horga, Samantha Halliwell, Royston Goodacre, Rainer Breitling, Neil Dixon
The apparent mislocalization or excretion of cytoplasmic proteins is a commonly observed phenomenon in both bacteria and eukaryotes. However, reports on the mechanistic basis and the cellular function of this so-called "nonclassical protein secretion" are limited. Here we report that protein overexpression in recombinant cells and antibiotic-induced translation stress in wild-type Escherichia coli cells both lead to excretion of cytoplasmic protein (ECP). Condition-specific metabolomic and proteomic analyses, combined with genetic knockouts, indicate a role for both the large mechanosensitive channel (MscL) and the alternative ribosome rescue factor A (ArfA) in ECP...
January 30, 2018: MBio
J B Lindström, N T Pierce, M I Latz
Transient receptor potential (TRP) ion channels are common components of mechanosensing pathways, mainly described in mammals and other multicellular organisms. To gain insight into the evolutionary origins of eukaryotic mechanosensory proteins, we investigated the involvement of TRP channels in mechanosensing in a unicellular eukaryotic protist, the dinoflagellate Lingulodinium polyedra. BLASTP analysis of the protein sequences predicted from the L. polyedra transcriptome revealed six sequences with high similarity to human TRPM2, TRPM8, TRPML2, TRPP1, and TRPP2; and characteristic TRP domains were identified in all sequences...
October 2017: Biological Bulletin
Alessandro Soloperto, Anna Boccaccio, Andrea Contestabile, Monica Moroni, Grace I Hallinan, Gemma Palazzolo, John Chad, Katrin Deinhardt, Dario Carugo, Francesco Difato
Development of remote stimulation techniques for neuronal tissues represents a challenging goal. Among the potential methods, mechanical stimuli are the most promising vector to convey information non-invasively into intact brain tissue. In this context, selective mechano-sensitization of neuronal circuits would pave the way to develop a new cell-type specific stimulation approach. We report here for the first time the development and characterization of mechano-sensitized neuronal networks through the heterologous expression of an engineered bacterial large conductance mechanosensitive ion channel (MscL)...
January 19, 2018: Journal of Cell Science
Martha Rocio Servin-Vences, Jessica Richardson, Gary R Lewin, Kate Poole
Cartilage tissue lines the joints of mammals, helping to lubricate joint movement and distribute mechanical loads. This tissue is comprised of isolated cells known as chondrocytes which are embedded in an extracellular matrix. Chondrocytes produce and maintain the cartilage by sensing and responding to changing mechanical loads. Mechanosensitive ion channels have been implicated in chondrocyte mechanotransduction and recent studies have shown that both PIEZO1 and TRPV4 can be activated by mechanical stimuli in these cells...
January 23, 2018: Clinical and Experimental Pharmacology & Physiology
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