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https://www.readbyqxmd.com/read/29331020/human-phenotypes-caused-by-piezo1-mutations-one-gene-two-overlapping-phenotypes
#1
Silvia Martin-Almedina, Sahar Mansour, Pia Ostergaard
PIEZO1 is a large mechanosensitive ion channel protein. Diseases associated with PIEZO1 include autosomal recessive Generalised Lymphatic Dysplasia of Fotiou (GLDF) and autosomal dominant Dehydrated Hereditary Stomatocytosis with or without pseudohyperkalemia and/or perinatal oedema (DHS). The two disorders show overlapping features, fetal hydrops/perinatal oedema have been reported in both. Electrophysiological studies suggest opposite mechanisms of action, the mutations identified in GLDF patients cause a loss-of-function mechanism of disease and mutations in DHS patients cause gain-of-function...
January 13, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29330322/cutting-edge-piezo1-mechanosensors-optimize-human-t-cell-activation
#2
Chinky Shiu Chen Liu, Deblina Raychaudhuri, Barnali Paul, Yogaditya Chakrabarty, Amrit Raj Ghosh, Oindrila Rahaman, Arindam Talukdar, Dipyaman Ganguly
TCRs recognize peptides on MHC molecules and induce downstream signaling, leading to activation and clonal expansion. In addition to the strength of the interaction of TCRs with peptides on MHC molecules, mechanical forces contribute to optimal T cell activation, as reflected by the superior efficiency of immobilized TCR-cross-linking Abs compared with soluble Abs in TCR triggering, although a dedicated mechanotransduction module is not identified. We found that the professional mechanosensor protein Piezo1 is critically involved in human T cell activation...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29261642/structure-of-the-mechanically-activated-ion-channel-piezo1
#3
Kei Saotome, Swetha E Murthy, Jennifer M Kefauver, Tess Whitwam, Ardem Patapoutian, Andrew B Ward
Piezo1 and Piezo2 are mechanically activated ion channels that mediate touch perception, proprioception and vascular development. Piezos are distinct from other ion channels and their structure remains poorly defined, impeding detailed study of their gating and ion permeation properties. Here we report a high-resolution cryo-electron microscopy structure of the mouse Piezo1 trimer. The detergent-solubilized complex adopts a three-blade propeller shape with a curved transmembrane region containing at least 26 transmembrane helices per protomer...
December 20, 2017: Nature
https://www.readbyqxmd.com/read/29259557/red-blood-cell-passage-of-small-capillaries-is-associated-with-transient-ca2-mediated-adaptations
#4
Jens G Danielczok, Emmanuel Terriac, Laura Hertz, Polina Petkova-Kirova, Franziska Lautenschläger, Matthias W Laschke, Lars Kaestner
When red blood cells (RBCs) pass constrictions or small capillaries they need to pass apertures falling well below their own cross section size. We used different means of mechanical stimulations (hypoosmotic swelling, local mechanical stimulation, passing through microfluidic constrictions) to observe cellular responses of human RBCs in terms of intracellular Ca2+-signaling by confocal microscopy of Fluo-4 loaded RBCs. We were able to confirm our in vitro results in a mouse dorsal skinfold chamber model showing a transiently increased intracellular Ca2+ when RBCs were passing through small capillaries in vivo...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29231809/structure-based-membrane-dome-mechanism-for-piezo-mechanosensitivity
#5
Yusong R Guo, Roderick MacKinnon
Mechanosensitive ion channels convert external mechanical stimuli into electrochemical signals for critical processes including touch sensation, balance, and cardiovascular regulation. The best understood mechanosensitive channel, MscL, opens a wide pore, which accounts for mechanosensitive gating due to in-plane area expansion. Eukaryotic Piezo channels have a narrow pore and therefore must capture mechanical forces to control gating in another way. We present a cryo-EM structure of mouse Piezo1 in a closed conformation at 3...
December 12, 2017: ELife
https://www.readbyqxmd.com/read/29225250/importance-of-the-average-glucose-level-and-estimated-glycated-hemoglobin-in-a-diabetic-patient-with-hereditary-hemolytic-anemia-and-liver-cirrhosis
#6
Rieko Nakatani, Takashi Murata, Takeshi Usui, Koki Moriyoshi, Toshiki Komeda, Yuichi Masuda, Maiko Kakita-Kobayashi, Tetsuya Tagami, Shinsaku Imashuku, Shigeo Kono, Kazunori Yamada, Akira Shimatsu
Glycated hemoglobin (HbA1c) is a widely used marker of glycemic control but can be affected by hemolytic anemia. Glycated albumin (GA) is also affected in patients with liver cirrhosis. We herein report the assessment of glycemic control in a 41-year-old man with dehydrated hereditary stomatocytosis and a PIEZO1 gene mutation complicated by diabetes mellitus and liver cirrhosis due to hemochromatosis. The estimated HbA1c calculated from the average glucose level obtained by continuous glucose monitoring or by self-monitoring of blood glucose was useful for evaluating the glycemic control in this patient, as HbA1c and GA were unreliable due to the coexisting conditions...
December 8, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29194632/endothelial-piezo1-channels-as-sensors-of-exercise
#7
David J Beech
Piezo1 channels are newly discovered ion channels which have come to the fore as players in endothelial biology. They have a key role as sensors of shear stress, a frictional force which arises in vascular biology because of blood flow. Endothelial Piezo1 channels are critical in murine embryonic development, just after the heart starts to beat and drive blood into the nascent endothelial network. In contrast they are not critical at the adult stage but they are important for performance in whole body physical activity where they have a vascular bed-specific effect to cause mesenteric resistance artery vasoconstriction, achieved through opposition to the vasodilatory mechanism of endothelium-derived hyperpolarization...
December 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29191841/piezo1-r1864h-rare-variant-accounts-for-a-genetic-phenotype-modifier-role-in-dehydrated-hereditary-stomatocytosis
#8
Immacolata Andolfo, Francesco Manna, Gianluca De Rosa, Barbara Eleni Rosato, Antonella Gambale, Giovanna Tomaiuolo, Antonio Carciati, Roberta Marra, Lucia De Franceschi, Achille Iolascon, Roberta Russo
No abstract text is available yet for this article.
November 30, 2017: Haematologica
https://www.readbyqxmd.com/read/29186675/inactivation-of-mechanically-activated-piezo1-ion-channels-is-determined-by-the-c-terminal-extracellular-domain-and-the-inner-pore-helix
#9
Jason Wu, Michael Young, Amanda H Lewis, Ashley N Martfeld, Breanna Kalmeta, Jörg Grandl
Piezo proteins form mechanically activated ion channels that are responsible for our sense of light touch, proprioception, and vascular blood flow. Upon activation by mechanical stimuli, Piezo channels rapidly inactivate in a voltage-dependent manner through an unknown mechanism. Inactivation of Piezo channels is physiologically important, as it modulates overall mechanical sensitivity, gives rise to frequency filtering of repetitive mechanical stimuli, and is itself the target of numerous human disease-related channelopathies that are not well understood mechanistically...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29176668/a-protein-interaction-mechanism-for-suppressing-the-mechanosensitive-piezo-channels
#10
Tingxin Zhang, Shaopeng Chi, Fan Jiang, Qiancheng Zhao, Bailong Xiao
Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmic-reticulum Ca2+ ATPase (SERCA), including the widely expressed SERCA2, as Piezo interacting proteins...
November 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/29171028/the-mechanosensitive-piezo1-channel-structural-features-and-molecular-bases-underlying-its-ion-permeation-and-mechanotransduction
#11
Yubo Wang, Bailong Xiao
The evolutionarily conserved Piezo family of proteins, including Piezo1 and Piezo2, encodes the long-sought-after mammalian mechanosensitive cation channels that play critical roles in various mechanotransduction processes such as touch, pain, proprioception, vascular development and blood pressure regulation. Mammalian Piezo proteins contain over 2500 amino acids with numerous predicted transmembrane segments, and do not bear sequence homology with any known class of ion channels. Thus, it is imperative, but challenging, to understand how they serve as effective mechanotransducers for converting mechanical force into electrochemical signals...
November 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29065102/the-function-of-the-novel-mechanical-activated-ion-channel-piezo1-in-the-human-osteosarcoma-cells
#12
Long Jiang, Yi-Ding Zhao, Wei-Xiang Chen
BACKGROUND The Piezo1 protein ion channel is a novel mechanical activated ion channel which is related to mechanical signal transduction. However, the function of the mechanically activated ion channel Piezo1 had not been explored. In this study, we explored the function of the Piezo1 ion channel in human osteosarcoma (OS) cells related to apoptosis, invasion, and the cell proliferation. MATERIAL AND METHODS Reverse transcription polymerase chain reaction (RT-PCR) and western-blotting were used to detect the expression of the Piezo1 protein...
October 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29057326/accelerating-metabolism-and-transmembrane-cation-flux-by-distorting-red-blood-cells
#13
Philip W Kuchel, Dmitry Shishmarev
Under static conditions, mammalian red blood cells (RBCs) require a continuous supply of energy, typically via glucose, to maintain their biconcave disc shape. Mechanical distortion, in a complementary way, should lead to increased energy demand that is manifest in accelerated glycolysis. The experimental challenge in observing this phenomenon was met by reversibly and reproducibly distorting the cells and noninvasively measuring glycolytic flux. This was done with a gel-distorting device that was coupled with (13)C nuclear magnetic resonance (NMR) spectroscopy...
October 2017: Science Advances
https://www.readbyqxmd.com/read/29051181/disorders-of-erythrocyte-hydration
#14
Patrick G Gallagher
The erythrocyte contains a network of pathways that regulate salt and water content in the face of extracellular and intracellular osmotic perturbations. This allows the erythrocyte to maintain a narrow range of cell hemoglobin concentration, a process critical for normal red blood cell function and survival. Primary disorders that perturb volume homeostasis jeopardize the erythrocyte and may lead to its premature destruction. These disorders are marked by clinical, laboratory, and physiologic heterogeneity...
October 19, 2017: Blood
https://www.readbyqxmd.com/read/29044106/a-mechanosensitive-ca-2-channel-activity-is-dependent-on-the-developmental-regulator-dek1
#15
Daniel Tran, Roberta Galletti, Enrique D Neumann, Annick Dubois, Reza Sharif-Naeini, Anja Geitmann, Jean-Marie Frachisse, Olivier Hamant, Gwyneth C Ingram
Responses of cells to mechanical stress are thought to be critical in coordinating growth and development. Consistent with this idea, mechanically activated channels play important roles in animal development. For example, the PIEZO1 channel controls cell division and epithelial-layer integrity and is necessary for vascular development in mammals. In plants, the actual contribution of mechanoperception to development remains questionable because very few putative mechanosensors have been identified and the phenotypes of the corresponding mutants are rather mild...
October 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28905417/investigating-the-structural-dynamics-of-the-piezo1-channel-activation-and-inactivation-by-coarse-grained-modeling
#16
Wenjun Zheng, Frederick Sachs
The PIEZO channels, a family of mechanosensitive channels in vertebrates, feature a fast activation by mechanical stimuli (eg, membrane tension) followed by a slower inactivation. Although a medium-resolution structure of the trimeric form of PIEZO1 was solved by cryo-electron microscopy (cryo-EM), key structural changes responsible for the channel activation and inactivation are still unknown. Toward decrypting the structural mechanism of the PIEZO1 activation and inactivation, we performed systematic coarse-grained modeling using an elastic network model and related modeling/analysis tools (ie, normal mode analysis, flexibility and hotspot analysis, correlation analysis, and cryo-EM-based hybrid modeling and flexible fitting)...
September 14, 2017: Proteins
https://www.readbyqxmd.com/read/28881406/the-circadian-expression-of-piezo1-trpv4-connexin26-and-vnut-associated-with-the-expression-levels-of-the-clock-genes-in-mouse-primary-cultured-urothelial-cells
#17
Tatsuya Ihara, Takahiko Mitsui, Yuki Nakamura, Mie Kanda, Sachiko Tsuchiya, Satoru Kira, Hiroshi Nakagomi, Norifumi Sawada, Yuri Hirayama, Keisuke Shibata, Eiji Shigetomi, Yoichi Shinozaki, Mitsuharu Yoshiyama, Atsuhito Nakao, Masayuki Takeda, Schuichi Koizumi
AIMS: To investigate circadian gene expressions in the mouse bladder urothelium to establish an experimental model and study the functions of the circadian rhythm. METHODS: The gene expression rhythms of the clock genes, mechano-sensors such as Piezo1 and TRPV4, ATP release mediated molecules (ARMM) such as Cx26 and VNUT were investigated in mouse primary cultured urothelial cells (UCs) of wild-type (WT) and Clock mutant (Clock(Δ19)(/Δ)(19) ) mice using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting analysis...
September 7, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28839146/piezo1-channels-sense-whole-body-physical-activity-to-reset-cardiovascular-homeostasis-and-enhance-performance
#18
Baptiste Rode, Jian Shi, Naima Endesh, Mark J Drinkhill, Peter J Webster, Sabine J Lotteau, Marc A Bailey, Nadira Y Yuldasheva, Melanie J Ludlow, Richard M Cubbon, Jing Li, T Simon Futers, Lara Morley, Hannah J Gaunt, Katarzyna Marszalek, Hema Viswambharan, Kevin Cuthbertson, Paul D Baxter, Richard Foster, Piruthivi Sukumar, Andrew Weightman, Sarah C Calaghan, Stephen B Wheatcroft, Mark T Kearney, David J Beech
Mammalian biology adapts to physical activity but the molecular mechanisms sensing the activity remain enigmatic. Recent studies have revealed how Piezo1 protein senses mechanical force to enable vascular development. Here, we address Piezo1 in adult endothelium, the major control site in physical activity. Mice without endothelial Piezo1 lack obvious phenotype but close inspection reveals a specific effect on endothelium-dependent relaxation in mesenteric resistance artery. Strikingly, the Piezo1 is required for elevated blood pressure during whole body physical activity but not blood pressure during inactivity...
August 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28749478/molecular-autopsy-in-maternal-fetal-medicine
#19
Hanan E Shamseldin, Wesam Kurdi, Fatima Almusafri, Maha Alnemer, Alya Alkaff, Zeneb Babay, Amal Alhashem, Maha Tulbah, Nada Alsahan, Rubina Khan, Bahauddin Sallout, Elham Al Mardawi, Mohamed Zain Seidahmed, Niema Meriki, Yasser Alsaber, Alya Qari, Ola Khalifa, Wafaa Eyaid, Zuhair Rahbeeni, Ahmed Kurdi, Mais Hashem, Tarfa Alshidi, Eman Al-Obeid, Firdous Abdulwahab, Niema Ibrahim, Nour Ewida, Karen El-Akouri, Mariam Al Mulla, Tawfeg Ben-Omran, Matthias Pergande, Sebahattin Cirak, Saeed Al Tala, Ranad Shaheen, Eissa Faqeih, Fowzan S Alkuraya
PurposeThe application of genomic sequencing to investigate unexplained death during early human development, a form of lethality likely enriched for severe Mendelian disorders, has been limited.MethodsIn this study, we employed exome sequencing as a molecular autopsy tool in a cohort of 44 families with at least one death or lethal fetal malformation at any stage of in utero development. Where no DNA was available from the fetus, we performed molecular autopsy by proxy, i.e., through parental testing.ResultsPathogenic or likely pathogenic variants were identified in 22 families (50%), and variants of unknown significance were identified in further 15 families (34%)...
July 27, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28731145/piezo1-protein-induces-the-apoptosis-of-human-osteoarthritis-derived-chondrocytes-by-activating-caspase-12-the-signaling-marker-of-er-stress
#20
Xiao-Fei Li, Zhao Zhang, Zhu-Ke Chen, Zhao-Wei Cui, Hai-Ning Zhang
The present study was carried out to determine whether the mechanically activated cation channel Piezo1 protein plays a role as a signaling pathway which causes the apoptosis of human chondrocytes. The chondrocytes were isolated, cultured, and then subjected to mechanical stretch force for 0, 2, 12, 24 and 48 h, respectively. The expression levels of Piezo1 and the apoptosis-related protein caspase-12 were assessed by reverse transcription-quantitative polymerase chain reaction, as well as the apoptosis-related genes, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-associated X protein (Bax) and Bcl-2-associated death promoter (BAD)...
September 2017: International Journal of Molecular Medicine
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