Read by QxMD icon Read


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
Charles D Cox, Chilman Bae, Lynn Ziegler, Silas Hartley, Vesna Nikolova-Krstevski, Paul R Rohde, Chai-Ann Ng, Frederick Sachs, Philip A Gottlieb, Boris Martinac
Mechanosensitive ion channels are force-transducing enzymes that couple mechanical stimuli to ion flux. Understanding the gating mechanism of mechanosensitive channels is challenging because the stimulus seen by the channel reflects forces shared between the membrane, cytoskeleton and extracellular matrix. Here we examine whether the mechanosensitive channel PIEZO1 is activated by force-transmission through the bilayer. To achieve this, we generate HEK293 cell membrane blebs largely free of cytoskeleton. Using the bacterial channel MscL, we calibrate the bilayer tension demonstrating that activation of MscL in blebs is identical to that in reconstituted bilayers...
2016: Nature Communications
Isabel Spier, Martin Kerick, Dmitriy Drichel, Sukanya Horpaopan, Janine Altmüller, Andreas Laner, Stefanie Holzapfel, Sophia Peters, Ronja Adam, Bixiao Zhao, Tim Becker, Richard P Lifton, Elke Holinski-Feder, Sven Perner, Holger Thiele, Markus M Nöthen, Per Hoffmann, Bernd Timmermann, Michal R Schweiger, Stefan Aretz
In up to 30% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, and POLE or POLD1, causing Polymerase-Proofreading-associated polyposis can be identified, although a hereditary etiology is likely. To uncover new causative genes, exome sequencing was performed using DNA from leukocytes and a total of 12 colorectal adenomas from seven unrelated patients with unexplained sporadic adenomatous polyposis...
April 2016: Familial Cancer
Amanda H Lewis, Jörg Grandl
Piezo1 ion channels mediate the conversion of mechanical forces into electrical signals and are critical for responsiveness to touch in metazoans. The apparent mechanical sensitivity of Piezo1 varies substantially across cellular environments, stimulating methods and protocols, raising the fundamental questions of what precise physical stimulus activates the channel and how its stimulus sensitivity is regulated. Here, we measured Piezo1 currents evoked by membrane stretch in three patch configurations, while simultaneously visualizing and measuring membrane geometry...
2015: ELife
Steven W Copp, Joyce S Kim, Victor Ruiz-Velasco, Marc P Kaufman
Mechanical and metabolic stimuli from contracting muscles evoke reflex increases in blood pressure, heart rate and sympathetic nerve activity. Little is known, however, about the nature of the mechano-gated channels on the thin fibre muscle afferents that contribute to evoke this reflex, termed the exercise pressor reflex. We determined the effect of GsMTx4, an inhibitor of mechano-gated Piezo channels, on the exercise pressor reflex evoked by intermittent contraction of the triceps surae muscles in decerebrated, unanaesthetized rats...
February 1, 2016: Journal of Physiology
Kevin Retailleau, Fabrice Duprat, Malika Arhatte, Sanjeev Sumant Ranade, Rémi Peyronnet, Joana Raquel Martins, Martine Jodar, Céline Moro, Stefan Offermanns, Yuanyi Feng, Sophie Demolombe, Amanda Patel, Eric Honoré
The mechanically activated non-selective cation channel Piezo1 is a determinant of vascular architecture during early development. Piezo1-deficient embryos die at midgestation with disorganized blood vessels. However, the role of stretch-activated ion channels (SACs) in arterial smooth muscle cells in the adult remains unknown. Here, we show that Piezo1 is highly expressed in myocytes of small-diameter arteries and that smooth-muscle-specific Piezo1 deletion fully impairs SAC activity. While Piezo1 is dispensable for the arterial myogenic tone, it is involved in the structural remodeling of small arteries...
November 10, 2015: Cell Reports
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"