scholarly journals Mechanosensitive Ion Channel Piezo1 Regulates Myocyte Fusion during Skeletal Myogenesis

2020 ◽  
Author(s):  
Huascar Pedro Ortuste Quiroga ◽  
Shingo Yokoyama ◽  
Massimo Ganassi ◽  
Kodai Nakamura ◽  
Tomohiro Yamashita ◽  
...  
Keyword(s):  
Ion Channel ◽  
Molecular Mechanisms ◽  
Myoblast Fusion ◽  
Mechanical Stimuli ◽  
Muscle Satellite Cell ◽  
Myotube Formation ◽  
Mechanosensitive Ion Channel ◽  
And Function ◽  
Sirna Knockdown

AbstractMechanical stimuli such as stretch and resistance training are essential to regulate growth and function of skeletal muscle. However, the molecular mechanisms involved in sensing mechanical stress remain unclear. Here, the purpose of this study was to investigate the role of the mechanosensitive ion channel Piezo1 during myogenic progression. Muscle satellite cell-derived myoblasts and myotubes were modified with stretch, siRNA knockdown and agonist-induced activation of Piezo1. Direct manipulation of Piezo1 modulates terminal myogenic progression. Piezo1 knockdown suppressed myoblast fusion during myotube formation and maturation. This was accompanied by downregulation of the fusogenic protein Myomaker. Piezo1 knockdown also lowered Ca2+ influx in response to stretch. Conversely Piezo1 activation stimulated fusion and increased Ca2+ influx in response to stretch. These evidences indicate that Piezo1 is essential for myotube formation and maturation, which may have implications for msucular dystrophy prevention through its role as a mechanosensitive Ca2+ channel.

scholarly journals The mechanosensitive ion channel Piezo2 mediates sensitivity to mechanical pain in mice

2018 ◽  
Vol 10 (462) ◽  
pp. eaat9897 ◽  
Author(s):  
Swetha E. Murthy ◽  
Meaghan C. Loud ◽  
Ihab Daou ◽  
Kara L. Marshall ◽  
Frederick Schwaller ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Sensory Neurons ◽  
Mechanical Allodynia ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Mechanical Stimuli ◽  
C Fiber ◽  
Mechanosensitive Ion Channel ◽  
Deficient Mice

The brush of a feather and a pinprick are perceived as distinct sensations because they are detected by discrete cutaneous sensory neurons. Inflammation or nerve injury can disrupt this sensory coding and result in maladaptive pain states, including mechanical allodynia, the development of pain in response to innocuous touch. However, the molecular mechanisms underlying the alteration of mechanical sensitization are poorly understood. In mice and humans, loss of mechanically activated PIEZO2 channels results in the inability to sense discriminative touch. However, the role of Piezo2 in acute and sensitized mechanical pain is not well defined. Here, we showed that optogenetic activation ofPiezo2-expressing sensory neurons induced nociception in mice. Mice lackingPiezo2in caudal sensory neurons had impaired nocifensive responses to mechanical stimuli. Consistently, ex vivo recordings in skin-nerve preparations from these mice showed diminished Aδ-nociceptor and C-fiber firing in response to mechanical stimulation. Punctate and dynamic allodynia in response to capsaicin-induced inflammation and spared nerve injury was absent in Piezo2-deficient mice. These results indicate that Piezo2 mediates inflammation- and nerve injury–induced sensitized mechanical pain, and suggest that targeting PIEZO2 might be an effective strategy for treating mechanical allodynia.

scholarly journals TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing

2018 ◽  
Author(s):  
L. Beaulieu-Laroche ◽  
M. Christin ◽  
AM Donoghue ◽  
F. Agosti ◽  
N. Yousefpour ◽  
...  
Keyword(s):  
Ion Channels ◽  
Heterologous Expression ◽  
Ion Channel ◽  
Behavioral Responses ◽  
Mechanical Stimuli ◽  
Thermal Pain ◽  
Fundamental Process ◽  
Mechanosensitive Ion Channel ◽  
Pain Stimuli ◽  
Essential Subunit

SummaryMechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying several physiological functions such as touch and pain sensing, hearing and proprioception. This process is carried out by specialized mechanosensitive ion channels whose identities have been discovered for most functions except pain sensing. Here we report the identification of TACAN (Tmem120A), an essential subunit of the mechanosensitive ion channel responsible for sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically-evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, knocking down TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to mechanical but not to thermal pain stimuli, without affecting the sensitivity to touch stimuli. We propose that TACAN is a pore-forming subunit of the mechanosensitive ion channel responsible for sensing mechanical pain.

scholarly journals Piezo1-Mediated Mechanotransduction Promotes Cardiac Hypertrophy by Impairing Calcium Homeostasis to Activate Calpain/Calcineurin Signaling

Hypertension ◽  
2021 ◽  
Author(s):  
Yuhao Zhang ◽  
Sheng-an Su ◽  
Wudi Li ◽  
Yuankun Ma ◽  
Jian Shen ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Ion Channel ◽  
Calcium Homeostasis ◽  
Pressure Overload ◽  
Cell Physiology ◽  
Hypertrophic Growth ◽  
Molecular Features ◽  
Mechanosensitive Ion Channel

Hemodynamic overload induces pathological cardiac hypertrophy, which is an independent risk factor for intractable heart failure in long run. Beyond neurohumoral regulation, mechanotransduction has been recently recognized as a major regulator of cardiac hypertrophy under a myriad of conditions. However, the identification and molecular features of mechanotransducer on cardiomyocytes are largely sparse. For the first time, we identified Piezo1 (Piezo type mechanosensitive ion channel component 1), a novel mechanosensitive ion channel with preference to Ca 2+ was remarkably upregulated under pressure overload and enriched near T-tubule and intercalated disc of cardiomyocyte. By applying cardiac conditional Piezo1 knockout mice (Piezo1 fl/fl Myh6Cre+, Piezo1 Cko ) undergoing transverse aortic constriction, we demonstrated that Piezo1 was required for the development of cardiac hypertrophy and subsequent adverse remodeling. Activation of Piezo1 by external mechanical stretch or agonist Yoda1 lead to the enlargement of cardiomyocytes in vitro, which was blocked by Piezo1 silencing or Yoda1 analog Dooku1 or Piezo1 inhibitor GsMTx4. Mechanistically, Piezo1 perturbed calcium homeostasis, mediating extracellular Ca 2+ influx and intracellular Ca 2+ overload, thereby increased the activation of Ca 2+ -dependent signaling, calcineurin, and calpain. Inhibition of calcineurin or calpain could abolished Yoda1 induced upregulation of hypertrophy markers and the hypertrophic growth of cardiomyocytes in vitro. From a comprehensive view of the cardiac transcriptome, most of Piezo1 affected genes were highly enriched in muscle cell physiology, tight junction, and corresponding signaling. This study characterizes an undefined role of Piezo1 in pressure overload induced cardiac hypertrophy. It may partially decipher the differential role of calcium under pathophysiological condition, implying a promising therapeutic target for cardiac dysfunction.

scholarly journals The role of Asprosin in patients with dilated cardiomyopathy

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ming-Shien Wen ◽  
Chao-Yung Wang ◽  
Jih-Kai Yeh ◽  
Chun-Chi Chen ◽  
Ming-Lung Tsai ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Mitochondrial Respiration ◽  
Cardiovascular Events ◽  
Molecular Mechanisms ◽  
Major Adverse Cardiovascular Events ◽  
Study Cohort ◽  
Protective Mechanisms ◽  
Mitochondrial Functions ◽  
And Function

Abstract Background Asprosin is a novel fasting glucogenic adipokine discovered in 2016. Asprosin induces rapid glucose releases from the liver. However, its molecular mechanisms and function are still unclear. Adaptation of energy substrates from fatty acid to glucose is recently considered a novel therapeutic target in heart failure treatment. We hypothesized that the asprosin is able to modulate cardiac mitochondrial functions and has important prognostic implications in dilated cardiomyopathy (DCM) patients. Methods We prospectively enrolled 50 patients (86% male, mean age 55 ± 13 years) with DCM and followed their 5-year major adverse cardiovascular events from 2012 to 2017. Comparing with healthy individuals, DCM patients had higher asprosin levels (191.2 versus 79.7 ng/mL, P < 0.01). Results During the 5-year follow-up in the study cohort, 16 (32.0%) patients experienced adverse cardiovascular events. Patients with lower asprosin levels (< 210 ng/mL) were associated with increased risks of adverse clinical outcomes with a hazard ratio of 7.94 (95% CI 1.88–33.50, P = 0.005) when compared patients with higher asprosin levels (≥ 210 ng/mL). Using cardiomyoblasts as a cellular model, we showed that asprosin prevented hypoxia-induced cell death and enhanced mitochondrial respiration and proton leak under hypoxia. Conclusions In patients with DCM, elevated plasma asprosin levels are associated with less adverse cardiovascular events in five years. The underlying protective mechanisms of asprosin may be linked to its functions relating to enhanced mitochondrial respiration under hypoxia.

New functions for old factors: the role of polyamines during the establishment of pregnancy

2019 ◽  
Vol 31 (7) ◽  
pp. 1228
Author(s):  
Jane C. Fenelon ◽  
Bruce D. Murphy
Keyword(s):  
Molecular Mechanisms ◽  
New Technologies ◽  
Alternative Pathway ◽  
Rapid Expansion ◽  
Polyamine Synthesis ◽  
Recent Developments ◽  
And Function ◽  
Implantation Period ◽  
Synthesis Regulation

Implantation is essential for the establishment of a successful pregnancy, and the preimplantation period plays a significant role in ensuring implantation occurs in a timely and coordinated manner. This requires effective maternal–embryonic signalling, established during the preimplantation period, to synchronise development. Although multiple factors have been identified as present during this time, the exact molecular mechanisms involved are unknown. Polyamines are small cationic molecules that are ubiquitously expressed from prokaryotes to eukaryotes. Despite being first identified over 300 years ago, their essential roles in cell proliferation and growth, including cancer, have only been recently recognised, with new technologies and interest resulting in rapid expansion of the polyamine field. This review provides a summary of our current understanding of polyamine synthesis, regulation and function with a focus on recent developments demonstrating the requirements for polyamines during the establishment of pregnancy up to the implantation stage, in particular the role of polyamines in the control of embryonic diapause and the identification of an alternative pathway for their synthesis in sheep pregnancy. This, along with other novel discoveries, provides new insights into the control of the peri-implantation period in mammals and highlights the complexities that exist in regulating this critical period of pregnancy.

The role of mitochondria in axonal degeneration and tissue repair in MS

2012 ◽  
Vol 18 (8) ◽  
pp. 1058-1067 ◽  
Author(s):  
J van Horssen ◽  
ME Witte ◽  
O Ciccarelli
Keyword(s):  
Mitochondrial Dysfunction ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Axonal Degeneration ◽  
Axonal Damage ◽  
Mitochondrial Metabolism ◽  
Imaging Studies ◽  
And Function

Axonal injury is a key feature of multiple sclerosis (MS) pathology and is currently seen as the main correlate for permanent clinical disability. Although little is known about the pathogenetic mechanisms that drive axonal damage and loss, there is accumulating evidence highlighting the central role of mitochondrial dysfunction in axonal degeneration and associated neurodegeneration. The aim of this topical review is to provide a concise overview on the involvement of mitochondrial dysfunction in axonal damage and destruction in MS. Hereto, we will discuss putative pathological mechanisms leading to mitochondrial dysfunction and recent imaging studies performed in vivo in patients with MS. Moreover, we will focus on molecular mechanisms and novel imaging studies that address the role of mitochondrial metabolism in tissue repair. Finally, we will briefly review therapeutic strategies aimed at improving mitochondrial metabolism and function under neuroinflammatory conditions.

Mo1594 - The Role of Piezo2 Mechanosensitive Ion Channel in Enterochromaffin (EC) Cell Mechanosensitivity

2018 ◽  
Vol 154 (6) ◽  
pp. S-764
Author(s):  
Constanza A. Alcaino Ayala ◽  
Kaitlyn R. Knutson ◽  
Gulcan Yildiz ◽  
David R. Linden ◽  
Joyce Li ◽  
...  
Keyword(s):  
Ion Channel ◽  
Mechanosensitive Ion Channel

scholarly journals Acetylated tubulin is essential for touch sensation in mice

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Shane J Morley ◽  
Yanmei Qi ◽  
Loredana Iovino ◽  
Laura Andolfi ◽  
Da Guo ◽  
...  
Keyword(s):  
Ion Channel ◽  
Sensory Neurons ◽  
Mechanical Energy ◽  
Mechanical Stimuli ◽  
Acetylated Tubulin ◽  
Fundamental Level ◽  
Tubulin Acetylation ◽  
Channel Opening ◽  
Mechanosensitive Ion Channel ◽  
Touch Sensation

At its most fundamental level, touch sensation requires the translation of mechanical energy into mechanosensitive ion channel opening, thereby generating electro-chemical signals. Our understanding of this process, especially how the cytoskeleton influences it, remains unknown. Here we demonstrate that mice lacking the α-tubulin acetyltransferase Atat1 in sensory neurons display profound deficits in their ability to detect mechanical stimuli. We show that all cutaneous afferent subtypes, including nociceptors have strongly reduced mechanosensitivity upon Atat1 deletion, and that consequently, mice are largely insensitive to mechanical touch and pain. We establish that this broad loss of mechanosensitivity is dependent upon the acetyltransferase activity of Atat1, which when absent leads to a decrease in cellular elasticity. By mimicking α-tubulin acetylation genetically, we show both cellular rigidity and mechanosensitivity can be restored in Atat1 deficient sensory neurons. Hence, our results indicate that by influencing cellular stiffness, α-tubulin acetylation sets the force required for touch.

scholarly journals Recent progress in research on molecular mechanisms of autophagy in the heart

2015 ◽  
Vol 308 (4) ◽  
pp. H259-H268 ◽  
Author(s):  
Yasuhiro Maejima ◽  
Yun Chen ◽  
Mitsuaki Isobe ◽  
Åsa B. Gustafsson ◽  
Richard N. Kitsis ◽  
...  
Keyword(s):  
Heart Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Degradation Process ◽  
Structure And Function ◽  
Cellular Functions ◽  
Evolutionarily Conserved ◽  
And Function ◽  
Cellular Dysfunction

Dysregulation of autophagy, an evolutionarily conserved process for degradation of long-lived proteins and organelles, has been implicated in the pathogenesis of human disease. Recent research has uncovered pathways that control autophagy in the heart and molecular mechanisms by which alterations in this process affect cardiac structure and function. Although initially thought to be a nonselective degradation process, autophagy, as it has become increasingly clear, can exhibit specificity in the degradation of molecules and organelles, such as mitochondria. Furthermore, it has been shown that autophagy is involved in a wide variety of previously unrecognized cellular functions, such as cell death and metabolism. A growing body of evidence suggests that deviation from appropriate levels of autophagy causes cellular dysfunction and death, which in turn leads to heart disease. Here, we review recent advances in understanding the role of autophagy in heart disease, highlight unsolved issues, and discuss the therapeutic potential of modulating autophagy in heart disease.

Homeostatic control of biological membranes by dedicated lipid and membrane packing sensors

2015 ◽  
Vol 396 (9-10) ◽  
pp. 1043-1058 ◽  
Author(s):  
Kristina Puth ◽  
Harald F. Hofbauer ◽  
James P. Sáenz ◽  
Robert Ernst
Keyword(s):  
Molecular Mechanisms ◽  
Biological Membranes ◽  
Homeostatic Control ◽  
Open Questions ◽  
Lipid Species ◽  
Sensor Proteins ◽  
And Function ◽  
Lipid Sensors ◽  
Role And Function

Abstract Biological membranes are dynamic and complex assemblies of lipids and proteins. Eukaryotic lipidomes encompass hundreds of distinct lipid species and we have only begun to understand their role and function. This review focuses on recent advances in the field of lipid sensors and discusses methodical approaches to identify and characterize putative sensor domains. We elaborate on the role of integral and conditionally membrane-associated sensor proteins, their molecular mechanisms, and identify open questions in the emerging field of membrane homeostasis.

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