Piezo2 Mediates Low-Threshold Mechanically Evoked Pain in the Cornea
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Genome Wide Association Study of Response to Interval and Continuous Exercise Training: the Predict‑HIIT Study Camilla J
Williams et al. J Biomed Sci (2021) 28:37 https://doi.org/10.1186/s12929-021-00733-7 RESEARCH Open Access Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study Camilla J. Williams1†, Zhixiu Li2†, Nicholas Harvey3,4†, Rodney A. Lea4, Brendon J. Gurd5, Jacob T. Bonafglia5, Ioannis Papadimitriou6, Macsue Jacques6, Ilaria Croci1,7,20, Dorthe Stensvold7, Ulrik Wislof1,7, Jenna L. Taylor1, Trishan Gajanand1, Emily R. Cox1, Joyce S. Ramos1,8, Robert G. Fassett1, Jonathan P. Little9, Monique E. Francois9, Christopher M. Hearon Jr10, Satyam Sarma10, Sylvan L. J. E. Janssen10,11, Emeline M. Van Craenenbroeck12, Paul Beckers12, Véronique A. Cornelissen13, Erin J. Howden14, Shelley E. Keating1, Xu Yan6,15, David J. Bishop6,16, Anja Bye7,17, Larisa M. Haupt4, Lyn R. Grifths4, Kevin J. Ashton3, Matthew A. Brown18, Luciana Torquati19, Nir Eynon6 and Jef S. Coombes1* Abstract Background: Low cardiorespiratory ftness (V̇O2peak) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O2peak, there is considerable inter-individual variability in the V̇O2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O2peak training response may improve personalisation of exercise programs. The aim of this study was to identify genetic variants that are associated with the magnitude of V̇O2peak response following exercise training. Methods: Participant change in objectively measured V̇O2peak from 18 diferent interventions was obtained from a multi-centre study (Predict-HIIT). A genome-wide association study was completed (n 507), and a polygenic predictor score (PPS) was developed using alleles from single nucleotide polymorphisms= (SNPs) signifcantly associ- –5 ated (P < 1 10 ) with the magnitude of V̇O2peak response. -
Using Drosophila to Study Mechanisms of Hereditary Hearing Loss Tongchao Li1,*, Hugo J
© 2018. Published by The Company of Biologists Ltd | Disease Models & Mechanisms (2018) 11, dmm031492. doi:10.1242/dmm.031492 REVIEW Using Drosophila to study mechanisms of hereditary hearing loss Tongchao Li1,*, Hugo J. Bellen1,2,3,4,5 and Andrew K. Groves1,3,5,‡ ABSTRACT Keats and Corey, 1999; Kimberling et al., 2010; Mathur and Yang, Johnston’s organ – the hearing organ of Drosophila – has a very 2015). It is an autosomal recessive genetic disease, characterized by different structure and morphology to that of the hearing organs of varying degrees of deafness and retinitis pigmentosa-induced vision vertebrates. Nevertheless, it is becoming clear that vertebrate and loss. Although our understanding of genetic hearing loss has invertebrate auditory organs share many physiological, molecular advanced greatly over the past 20 years (Vona et al., 2015), there is a and genetic similarities. Here, we compare the molecular and cellular pressing need for experimental systems to understand the function features of hearing organs in Drosophila with those of vertebrates, of the proteins encoded by deafness genes. The mouse is well and discuss recent evidence concerning the functional conservation established as a model for studying human genetic deafness (Brown of Usher proteins between flies and mammals. Mutations in Usher et al., 2008), but other model organisms, such as the fruit fly genes cause Usher syndrome, the leading cause of human deafness Drosophila, might also provide convenient and more rapid ways to and blindness. In Drosophila, some Usher syndrome proteins appear assay the function of candidate deafness genes. to physically interact in protein complexes that are similar to those In mammals, mechanosensitive hair cells reside in a specialized described in mammals. -
Novel Mutations in TPM2 and PIEZO2 Are Responsible for Distal
Li et al. BMC Medical Genetics (2018) 19:179 https://doi.org/10.1186/s12881-018-0692-8 RESEARCH ARTICLE Open Access Novel mutations in TPM2 and PIEZO2 are responsible for distal arthrogryposis (DA) 2B and mild DA in two Chinese families Shan Li1†, Yi You1†, Jinsong Gao2, Bin Mao1, Yixuan Cao1, Xiuli Zhao1* and Xue Zhang1* Abstract Background: Distal arthrogryposis (DA) is a group of clinically and genetically heterogeneous disorders that involve multiple congenital limb contractures and comprise at least 10 clinical subtypes. Here, we describe our findings in two Chinese families: Family 1 with DA2B (MIM 601680) and Family 2 with mild DA. Methods: To map the disease locus, two-point linkage analysis was performed with microsatellite markers closed to TPM2, TNNI2/TNNT3 and TNNC2. In Family 1, a positive LOD (logarithm of odds) score was only obtained at the microsatellite marker close to TPM2 and mutation screening was performed using direct sequencing of TPM2 in the proband. In Family 2, for the LOD score that did not favor linkage to any markers, whole-exome sequencing (WES) was performed on the proband. PCR–restriction fragment length polymorphism (RFLP) and bioinformatics analysis were then applied to identify the pathogenic mutations in two families. In order to correlate genotype with phenotype in DA, retrospective analyses of phenotypic features according to the TPM2 and PIEZO2 mutation spectrums were carried out. Results: A heterozygous missense mutation c.308A > G (p.Q103R) in TPM2 in Family 1, and a novel variation c.8153G > A (p.R2718Q) in PIEZO2 in Family 2 were identified. -
The Function and Regulation of Piezo Ion Channels Jason Wu,1 Amanda[13 TD$IF]H
TIBS 1305 No. of Pages 15 Series: Fresh Perspectives from Emerging Experts Review Touch, Tension, and Transduction – The Function and Regulation of Piezo Ion Channels Jason Wu,1 Amanda[13_TD$IF]H. Lewis,1 and Jörg Grandl1,* In 2010, two proteins, Piezo1 and Piezo2, were identified as the long-sought Trends molecular carriers of an excitatory mechanically activated current found in many Piezo proteins were identified in 2010 cells. This discovery has opened the floodgates for studying a vast number of as the pore-forming subunits of excita- mechanotransduction processes. Over the past 6 years, groundbreaking tory mechanosensitive ion channels. research has identified Piezos as ion channels that sense light touch, proprio- Piezo ion channels play essential roles ception, and vascular blood flow, ruled out roles for Piezos in several other in diverse physiological processes ran- mechanotransduction processes, and revealed the basic structural and func- ging from regulation of red blood cell fi volume to sensation of gentle touch, tional properties of the channel. Here, we review these ndings and discuss the and are associated with a number of many aspects of Piezo function that remain mysterious, including how Piezos diseases. convert a variety of mechanical stimuli into channel activation and subsequent A recent medium-resolution structure inactivation, and what molecules and mechanisms modulate Piezo function. gives insight into the overall architec- ture of Piezo1, but does not give straight answers as to how the channel Piezo Proteins: True Mechanically Activated Ion Channels? transduces mechanical force into pore Piezo proteins are pore-forming subunits of ion channels that open in response to mechanical opening. -
High-Throughput Controlled Mechanical Stimulation and Functional
bioRxiv preprint doi: https://doi.org/10.1101/107318; this version posted February 10, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 2 3 4 High-Throughput Controlled Mechanical Stimulation and Functional 5 Imaging In Vivo 6 7 Yongmin Cho1*, Daniel A. Porto2*, Hyundoo Hwang1, Laura J. Grundy3, 8 William R. Schafer3, Hang Lu1,2 9 10 1School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, USA 11 2Interdisciplinary Bioengineering Program, Georgia Institute of Technology, USA 12 3Medical Research Council Laboratory of Molecular Biology, Cambridge, UK 13 *These authors contributed equally to this work. 14 15 Correspondence should be addressed to HL: [email protected], 1-404-894-8473 16 17 18 19 20 21 1 bioRxiv preprint doi: https://doi.org/10.1101/107318; this version posted February 10, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 22 Abstract: 23 24 Understanding mechanosensation and other sensory behavior in genetic model systems such as 25 C. elegans is relevant to many human diseases. These studies conventionally require 26 immobilization by glue and manual delivery of stimuli, leading to low experimental throughput 27 and high variability. Here we present a microfluidic platform that delivers precise mechanical 28 stimuli robustly. -
1 Piezo2 Mechanosensitive Ion Channel Is Located to Sensory
bioRxiv preprint doi: https://doi.org/10.1101/2021.01.20.427483; this version posted January 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Piezo2 mechanosensitive ion channel is located to sensory neurons and non-neuronal cells in rat peripheral sensory pathway: implications in pain Seung Min Shin1, Francie Moehring2, Brandon Itson-Zoske1, Fan Fan3, Cheryl L. Stucky2, Quinn H. Hogan1, 4, and Hongwei Yu1, 4* 1. Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226 2. Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226 3. Department of Pharmacology and Toxicology, Mississippi University Medical Center, Jackson, Mississippi 39216 4. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295 * Correspondence author: [email protected], phone: 414-955-5745 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.20.427483; this version posted January 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Piezo2 mechanotransduction channel is a crucial mediator of sensory neurons for sensing and transducing touch, vibration, and proprioception. We here characterized Piezo2 expression and cell specificity in rat peripheral sensory pathway using a validated Piezo2 antibody. Immunohistochemistry using this antibody revealed Piezo2 expression in pan primary sensory neurons (PSNs) of dorsal rood ganglia (DRG) in naïve rats, which was actively transported along afferent axons to both central presynaptic terminals innervating the spinal dorsal horn (DH) and peripheral afferent terminals in skin. -
Centre for Arab Genomic Studies a Division of Sheikh Hamdan Award for Medical Sciences
Centre for Arab Genomic Studies A Division of Sheikh Hamdan Award for Medical Sciences The Catalogue for Transmission Genetics in Arabs CTGA Database Piezo-Type Mechanosensitive Ion Channel Component 2 Alternative Names autosomal recessive disorder of Distal PIEZO2 Arthrogryposis with Impaired Proprioception and Family with Sequence Similarity 38, Member B Touch (DAIPT). FAM38B Molecular Genetics Record Category The PIEZO2 gene is located on the short arm of Gene locus chromosome 18. It spans a length of 482 kb of DNA and its coding sequence is spread across 55 WHO-ICD exons. The protein product encoded by this gene N/A to gene loci has a molecular mass of 318 kDa and consists of 2752 amino acids. Several additional isoforms of Incidence per 100,000 Live Births the PIEZO2 protein exist due to alternatively N/A to gene loci spliced transcript variants. The gene is found to be overexpressed in the brain, spinal cord, pancreas, OMIM Number liver and lung. Heterozygous mutations in the 613629 PIEZO2 gene, including missense variants and deletions, have been linked to the disorders of Mode of Inheritance MWKS, DA3 and DA5. So far only one mutation N/A to gene loci (R2686C) has been identified in MWKS. Homozygous and compound heterozygous Gene Map Locus mutations in the gene associated with Distal 18p11.22-p11.21 Arthrogryposis, with Impaired Proprioception and Touch (DAIPT) mainly include nonsense variants Description and deletions that cause frameshift and premature The PIEZO2 gene encodes a large protein truncation, often resulting in a non-functioning containing 31 transmembrane domains. This protein PIEZO2 protein. -
Mechanosensation* Miriam B
Mechanosensation* Miriam B. Goodman§, Department of Molecular and Cellular Physiology, School of Medicine-Stanford University, Stanford, CA 94305-5345 USA Table of Contents 1. Introduction ............................................................................................................................1 2. C. elegans mechanoreceptor neurons ........................................................................................... 2 2.1. Nonciliated MRNs ......................................................................................................... 2 2.2. Ciliated MRNs .............................................................................................................. 5 3. Neural circuits linking mechanosensation to locomotion .................................................................. 7 4. Molecules and mechanisms of mechanotransduction ....................................................................... 7 5. Conclusions .......................................................................................................................... 10 6. Acknowledgements ................................................................................................................ 10 7. References ............................................................................................................................ 10 Abstract Wild C. elegans and other nematodes live in dirt and eat bacteria, relying on mechanoreceptor neurons (MRNs) to detect collisions with soil particles and other animals as -
Molecular Mechanisms of Mechanotransduction in Mammalian Sensory Neurons
REVIEWS Molecular mechanisms of mechanotransduction in mammalian sensory neurons Patrick Delmas, Jizhe Hao and Lise Rodat-Despoix Abstract | The somatosensory system mediates fundamental physiological functions, including the senses of touch, pain and proprioception. This variety of functions is matched by a diverse array of mechanosensory neurons that respond to force in a specific fashion. Mechanotransduction begins at the sensory nerve endings, which rapidly transform mechanical forces into electrical signals. Progress has been made in establishing the functional properties of mechanoreceptors, but it has been remarkably difficult to characterize mechanotranducer channels at the molecular level. However, in the past few years, new functional assays have provided insights into the basic properties and molecular identity of mechanotransducer channels in mammalian sensory neurons. The recent identification of novel families of proteins as mechanosensing molecules will undoubtedly accelerate our understanding of mechanotransduction mechanisms in mammalian somatosensation. mechanoreceptors Mechanoreceptor The ability of living organisms to perceive mechanical The ability of to detect mechanical A sensory receptor that forces is crucial for interacting with the physical world. cues relies on the presence of mechanotranducer channels responds to mechanical Mechanotransduction, the conversion of a mechanical on sensory nerve endings that rapidly transform pressure or distortion by causing stimulus into a biological response, constitutes the basis mechanical forces into electrical signals and depolarize membrane depolarization and action potential firing. of fundamental physiological processes, such as the the receptive field; this local depolarization, called the senses of touch, balance, proprioception and hearing, receptor potential, can generate action potentials that Mechanotransducer channel and makes a vital contribution to homeostasis. propagate towards the CNS. -
Touching Upon Regulators of Piezo2 in Mouse Somatosensation
Touching upon regulators of Piezo2 in mouse somatosensation Dissertation for the award of the degree “Doctor rerum naturalium” (Dr.rer.nat.) of the Georg-August-Universität Göttingen within the International Max Planck Research School (IMPRS), Neuroscience of the Georg-August University School of Science (GAUSS) submitted by Pratibha Narayanan from New Delhi Göttingen, 2017 Thesis Committee Dr. Manuela Schmidt Somatosensory signaling and Systems Biology group, Max Planck Institute for Experimental Medicine Prof. Dr. Martin Göpfert Dept. of Cellular Neurobiology, Schwann- Schleiden Research Centre Prof. Dr. Luis A. Pardo Dept. of Molecular Biology of Neuronal Signals, Max Planck Institute for Experimental Medicine Members of the Examination Board Dr. Manuela Schmidt Somatosensory signaling and Systems Biology group, Max Planck Institute for Experimental Medicine Prof. Dr. Martin Göpfert Dept. of Cellular Neurobiology, Schwann- Schleiden Research Centre Further members of the Examination Board Prof. Dr. Luis A. Pardo Dept. of Molecular Biology of Neuronal Signals, Max Planck Institute of Experimental Medicine Prof. Dr. Tobias Moser Institute for Auditory Neuroscience & InnerEarLab Prof. Dr. Silvio O. Rizzoli Dept. of Neuro-and Sensory Physiology, University Medical Center Prof. Dr. Michael Sereda Molecular and Translational Neurology group, Max Planck Institute for Experimental Medicine Date of oral examination: 23 November 2017 TABLE OF CONTENTS List of figures.............................................................................................. -
Unlocking the Molecular Mechanisms Behind Our Sense of Touch INNER WORKINGS Leah Shaffer, Science Writer
INNER WORKINGS Unlocking the molecular mechanisms behind our sense of touch INNER WORKINGS Leah Shaffer, Science Writer Molecular biologists don’t typically conduct their re- molecular mechanisms underlying the enigmatic sense search knee deep in muck, checking underground traps of touch. for an elusive mole. But Diana Bautista needed those Scientists are on the hunt for the ion channels or any moles to help her understand the mysterious underpin- signaling molecules involved in touch sensation. Thus nings of humans’ sense of touch. “The mechanisms that far, these discoveries provide only a small window drive mechanical hypersensitivity and mechanical sens- into the complex machinery of mechanosensation. ing have been really, a big black box in the field,” says Still, any step closer to mastering the circuitry that Bautista, an associate professor of cell and develop- controls mechanical pain is a welcome development mental biology at University of California, Berkeley. for patients and physicians overly reliant on poten- Bautista’s quarry, the star-nose mole, offers a rare op- tially addictive opioids. And mechanosensation re- portunity to study a sense of touch few other creatures search goes far beyond touch and pain. Scientists are possess. The mole’s centimeter-sized touch organ (the star discovering that mechanosensory channels play a of tentacles on its face) is bedecked with 100,000 nerve crucial role in the very function of internal organs. fibers, called mechanonociceptors. That is five times the number of fibers on a human hand (1). Mechano- A Sense of Place nociceptors are the first step in the journey of sending a A basic understanding of the sense of touch has been touch signal to the brain. -
Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act As Important Regulators of Lymphatic Development and Function
International Journal of Molecular Sciences Review Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function László Bálint and Zoltán Jakus * Department of Physiology, Semmelweis University School of Medicine, 1094 Budapest, Hungary; [email protected] * Correspondence: [email protected] Abstract: Our understanding of the function and development of the lymphatic system is expanding rapidly due to the identification of specific molecular markers and the availability of novel genetic approaches. In connection, it has been demonstrated that mechanical forces contribute to the en- dothelial cell fate commitment and play a critical role in influencing lymphatic endothelial cell shape and alignment by promoting sprouting, development, maturation of the lymphatic network, and coordinating lymphatic valve morphogenesis and the stabilization of lymphatic valves. However, the mechanosignaling and mechanotransduction pathways involved in these processes are poorly understood. Here, we provide an overview of the impact of mechanical forces on lymphatics and sum- marize the current understanding of the molecular mechanisms involved in the mechanosensation and mechanotransduction by lymphatic endothelial cells. We also discuss how these mechanosen- sitive pathways affect endothelial cell fate and regulate lymphatic development and function. A Citation: Bálint, L.; Jakus, Z. Mechanosensation and better understanding of these mechanisms may provide a deeper insight into the pathophysiology Mechanotransduction by Lymphatic of various diseases associated with impaired lymphatic function, such as lymphedema and may Endothelial Cells Act as Important eventually lead to the discovery of novel therapeutic targets for these conditions. Regulators of Lymphatic Development and Function. Int. J. Keywords: lymphatics; lymphatic development; lymphatic function; mechanical forces; mechanosen- Mol.