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Ruhma Syeda, Maria N Florendo, Charles D Cox, Jennifer M Kefauver, Jose S Santos, Boris Martinac, Ardem Patapoutian
The conversion of mechanical force to chemical signals is critical for many biological processes, including the senses of touch, pain, and hearing. Mechanosensitive ion channels play a key role in sensing the mechanical stimuli experienced by various cell types and are present in organisms from bacteria to mammals. Bacterial mechanosensitive channels are characterized thoroughly, but less is known about their counterparts in vertebrates. Piezos have been recently established as ion channels required for mechanotransduction in disparate cell types in vitro and in vivo...
November 8, 2016: Cell Reports
ShengPeng Wang, Ramesh Chennupati, Harmandeep Kaur, Andras Iring, Nina Wettschureck, Stefan Offermanns
Arterial blood pressure is controlled by vasodilatory factors such as nitric oxide (NO) that are released from the endothelium under the influence of fluid shear stress exerted by flowing blood. Flow-induced endothelial release of ATP and subsequent activation of Gq/G11-coupled purinergic P2Y2 receptors have been shown to mediate fluid shear stress-induced stimulation of NO formation. However, the mechanism by which fluid shear stress initiates these processes is unclear. Here, we have shown that the endothelial mechanosensitive cation channel PIEZO1 is required for flow-induced ATP release and subsequent P2Y2/Gq/G11-mediated activation of downstream signaling that results in phosphorylation and activation of AKT and endothelial NOS...
December 1, 2016: Journal of Clinical Investigation
François Seghers, Xavier Yerna, Nadège Zanou, Olivier Devuyst, Rudi Vennekens, Bernd Nilius, Philippe Gailly
KEY POINTS: Increase in blood pressure in the renal afferent arteriole is known to induce an increase in cytosolic calcium concentration ([Ca(2+) ]i ) of juxtaglomerular (JG) cells and to result in a decreased secretion of renin. Mechanical stimulation of As4.1 JG cells induces an increase in [Ca(2+) ]i that is inhibited by HC067047 and RN1734, two inhibitors of TRPV4, or by siRNA-mediated repression of TRPV4. Inhibition of TRPV4 impairs pressure-induced decrease in renin secretion. Compared to wild-type mice, Trpv4(-/-) mice present increased resting plasma levels of renin and aldosterone and present a significantly altered pressure-renin relationship...
October 25, 2016: Journal of Physiology
Immacolata Andolfo, Roberta Russo, Antonella Gambale, Achille Iolascon
After the first proposed model of the red blood cell membrane skeleton 36 years ago, several additional proteins have been discovered during the intervening years, and their relationship with the pathogenesis of the related disorders have been somewhat defined. The knowledge of erythrocyte membrane structure is important because it represents the model for spectrin-based membrane skeletons in all cells and because defects in its structure underlie multiple hemolytic anemias. This review summarizes the main features of erythrocyte membrane disorders, dividing them into structural and altered permeability defects, focusing particularly on the most recent advances...
November 2016: Haematologica
Mai Michishita, Kazuo Yano, Ken-Ichi Tomita, Osamu Matsuzaki, Ken-Ichi Kasahara
AIMS: For patients with benign prostatic hyperplasia (BPH), storage symptoms due to bladder dysfunction are bothersome, and that mechanism elucidation is needed. Piezo1, a mechanically activated ion channel, is believed to play a role in sensing bladder distension. To investigate the involvement of Piezo1 in bladder dysfunction, we examined the expression and distribution of Piezo1 and neurofilament (NF-L) to understand pathological alterations in rat bladders with partial bladder outlet obstruction (pBOO), an animal model of BPH...
October 15, 2016: Life Sciences
Jason Wu, Amanda H Lewis, Jörg Grandl
In 2010, two proteins, Piezo1 and Piezo2, were identified as the long-sought molecular carriers of an excitatory mechanically activated current found in many cells. This discovery has opened the floodgates for studying a vast number of mechanotransduction processes. Over the past 6 years, groundbreaking research has identified Piezos as ion channels that sense light touch, proprioception, and vascular blood flow, ruled out roles for Piezos in several other mechanotransduction processes, and revealed the basic structural and functional properties of the channel...
October 12, 2016: Trends in Biochemical Sciences
Jason Wu, Raman Goyal, Jörg Grandl
Piezos are mechanically activated ion channels that function as sensors of touch and pressure in various cell types. However, the precise mechanism and structures mediating mechanical activation and subsequent inactivation have not yet been identified. Here we use magnetic nanoparticles as localized transducers of mechanical force in combination with pressure-clamp electrophysiology to identify mechanically sensitive domains important for activation and inactivation.
October 3, 2016: Nature Communications
David E Koser, Amelia J Thompson, Sarah K Foster, Asha Dwivedy, Eva K Pillai, Graham K Sheridan, Hanno Svoboda, Matheus Viana, Luciano da F Costa, Jochen Guck, Christine E Holt, Kristian Franze
During nervous system development, neurons extend axons along well-defined pathways. The current understanding of axon pathfinding is based mainly on chemical signaling. However, growing neurons interact not only chemically but also mechanically with their environment. Here we identify mechanical signals as important regulators of axon pathfinding. In vitro, substrate stiffness determined growth patterns of Xenopus retinal ganglion cell axons. In vivo atomic force microscopy revealed a noticeable pattern of stiffness gradients in the embryonic brain...
September 19, 2016: Nature Neuroscience
X F Li, Z Zhang, X D Li, T B Wang, H N Zhang
OBJECTIVE: To invstigate the mechanism of new mechanically-activated cation channel protein (Piezo1) can cause the apoptosis of the human chondrocytes under compressive loading, using a Flexercell unit by activating classical Mitogen-activated protein kinase (MAPK) signal pathyway(ERK1/2). METHODS: Primary human chondrocytes were isolated, cultured, and then subjected to the static compressive loading for 0, 2, 12, 24, 48 h, respectively.The expressions of Piezo1 and the ERK1/2 were assessed by reverse transcription-polymerase chain reaction(PT-PCR), as well as the apoptosis gene B cell lymphoma/leukemia-2(Bcl-2) Bel-associated X protein(Bax)...
August 16, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Lingzhi Huang, Lezhi Li, Xiaofang Chen, Huiling Zhang, Zeya Shi
BACKGROUND: Acute myocardial infarction (AMI) is commonly known as the heart attack. The molecular events involved in the development of AMI remain unclear. This study was to investigate the expression of miR-103a in patients with high blood pressure (HBP) and AMI patients with and without HBP, as well as its effect on endothelial cell functions. METHODS: MiR-103a expression in plasma and peripheral blood mononuclear cells was measured by real-time polymerase chain reaction (PCR)...
August 12, 2016: Cardiology Journal
Catherine Badens, Hélène Guizouarn
Genetic defects of erythrocyte transport proteins cause disorders of red blood cell volume that are characterized by abnormal permeability to the cations Na(+) and K(+) and, consequently, by changes in red cell hydration. Clinically, these disorders are associated with chronic haemolytic anaemia of variable severity and significant co-morbidities, such as iron overload. This review provides an overview of recent insights into the molecular basis of this group of rare anaemias involving cation channels and transporters dysfunction...
September 2016: British Journal of Haematology
Gyu-Sang Hong, Byeongjun Lee, Jungwon Wee, Hyeyeon Chun, Hyungsup Kim, Jooyoung Jung, Joo Young Cha, Tae-Ryong Riew, Gyu Hyun Kim, In-Beom Kim, Uhtaek Oh
Touch sensation or proprioception requires the transduction of mechanical stimuli into electrical signals by mechanoreceptors in the periphery. These mechanoreceptors are equipped with various transducer channels. Although Piezo1 and 2 are mechanically activated (MA) channels with rapid inactivation, MA molecules with other inactivation kinetics have not been identified. Here we report that heterologously expressed Tentonin3 (TTN3)/TMEM150C is activated by mechanical stimuli with distinctly slow inactivation kinetics...
July 6, 2016: Neuron
X Z Shawn Xu
Mechanosensitive channels mediate touch, hearing, proprioception, and blood pressure regulation. Piezo proteins, including Piezo1 and Piezo2, represent a new class of mechanosensitive channels that have been reported to play key roles in most, if not all, of these modalities. The structural architecture and molecular mechanisms by which Piezos act as mechanosensitive channels, however, remain mysterious. Two new studies have now provided critical insights into the atomic structure and molecular basis of the ion permeation and mechano-gating properties of the Piezo1 channel...
June 2016: Neuroscience Bulletin
Wei-Chien Hung, Jessica R Yang, Christopher L Yankaskas, Bin Sheng Wong, Pei-Hsun Wu, Carlos Pardo-Pastor, Selma A Serra, Meng-Jung Chiang, Zhizhan Gu, Denis Wirtz, Miguel A Valverde, Joy T Yang, Jin Zhang, Konstantinos Konstantopoulos
Cells adopt distinct signaling pathways to optimize cell locomotion in different physical microenvironments. However, the underlying mechanism that enables cells to sense and respond to physical confinement is unknown. Using microfabricated devices and substrate-printing methods along with FRET-based biosensors, we report that, as cells transition from unconfined to confined spaces, intracellular Ca(2+) level is increased, leading to phosphodiesterase 1 (PDE1)-dependent suppression of PKA activity. This Ca(2+) elevation requires Piezo1, a stretch-activated cation channel...
May 17, 2016: Cell Reports
Joana Raquel Martins, David Penton, Rémi Peyronnet, Malika Arhatte, Céline Moro, Nicolas Picard, Birgül Kurt, Amanda Patel, Eric Honoré, Sophie Demolombe
The collecting duct (CD) is the final segment of the kidney involved in the fine regulation of osmotic and ionic balance. During dehydration, arginine vasopressin (AVP) stimulates the expression and trafficking of aquaporin 2 (AQP2) to the apical membrane of CD principal cells, thereby allowing water reabsorption from the primary urine. Conversely, when the secretion of AVP is lowered, as for instance upon water ingestion or as a consequence of diabetes insipidus, the CD remains water impermeable leading to enhanced diuresis and urine dilution...
July 2016: Pflügers Archiv: European Journal of Physiology
Shinsaku Imashuku, Hideki Muramatsu, Takashi Sugihara, Yusuke Okuno, Xinan Wang, Kenichi Yoshida, Ayako Kato, Koichi Kato, Yasuaki Tatsumi, Ai Hattori, Shinya Kita, Keishi Oe, Atsushi Sueyoshi, Takeshi Usui, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Seiji Kojima, Hitoshi Kanno
Hereditary xerocytosis (HX) or dehydrated hereditary stomatocytosis (DHS) [OMIM 194380], in which PIEZO1 gene mutation has recently been identified, is difficult to diagnose. We report here the discovery of a PIEZO1 gene mutation in a Japanese family (father, daughter, and son) who were previously diagnosed with hereditary high phosphatidylcholine hemolytic anemia (HPCHA). All of the affected family members had non-spherocytic hemolytic anemia associated with severe hemochromatosis-related diabetes mellitus...
July 2016: International Journal of Hematology
Chilman Bae, Thomas M Suchyna, Lynn Ziegler, Frederick Sachs, Philip A Gottlieb
PIEZO1 is a mechanosensitive eukaryotic cation-selective channel that rapidly inactivates in a voltage-dependent manner. We previously showed that a fluorescent protein could be encoded within the hPIEZO1 sequence without loss of function. In this work, we split the channel into two at this site and asked if coexpression would produce a functional channel or whether gating and permeation might be contained in either segment. The split protein was expressed in two segments by a bicistronic plasmid where the first segment spanned residues 1 to 1591, and the second segment spanned 1592 to 2521...
2016: PloS One
Qiancheng Zhao, Kun Wu, Jie Geng, Shaopeng Chi, Yanfeng Wang, Peng Zhi, Mingmin Zhang, Bailong Xiao
Piezo proteins have been proposed as the long-sought-after mechanosensitive cation channels in mammals that play critical roles in various mechanotransduction processes. However, the molecular bases that underlie their ion permeation and mechanotransduction have remained functionally undefined. Here we report our finding of the miniature pore-forming module of Piezo1 that resembles the pore architecture of other trimeric channels and encodes the essential pore properties. We further identified specific residues within the pore module that determine unitary conductance, pore blockage and ion selectivity for divalent and monovalent cations and anions...
March 16, 2016: Neuron
Laura F Corns, Walter Marcotti
The mechanoelectrical transducer (MET) channels located at the stereocilia tip of cochlear hair cells are crucial to convert the mechanical energy of sound into receptor potentials, but the identity of its pore-forming subunits remains uncertain. Piezo1, which has been identified in the transcriptome of mammalian cochlear hair cells, encodes a transmembrane protein that forms mechanosensitive channels in other tissues. We investigated the properties of the MET channel in outer hair cells (OHCs) of Piezo1 mice (postnatal day 6-9)...
February 2016: Physiological Reports
Elizabeth S Zuccala, Timothy J Satchwell, Fiona Angrisano, Yan Hong Tan, Marieangela C Wilson, Kate J Heesom, Jake Baum
The invasive blood-stage malaria parasite - the merozoite - induces rapid morphological changes to the target erythrocyte during entry. However, evidence for active molecular changes in the host cell that accompany merozoite invasion is lacking. Here, we use invasion inhibition assays, erythrocyte resealing and high-definition imaging to explore red cell responses during invasion. We show that although merozoite entry does not involve erythrocyte actin reorganisation, it does require ATP to complete the process...
2016: Scientific Reports
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