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Andrea Delle Vedove, Markus Storbeck, Raoul Heller, Irmgard Hölker, Malavika Hebbar, Anju Shukla, Olafur Magnusson, Sebahattin Cirak, Katta M Girisha, Mary O'Driscoll, Bart Loeys, Brunhilde Wirth
No abstract text is available yet for this article.
December 1, 2016: American Journal of Human Genetics
Zizhen Wu, Nicolas Grillet, Bo Zhao, Christopher Cunningham, Sarah Harkins-Perry, Bertrand Coste, Sanjeev Ranade, Navid Zebarjadi, Maryline Beurg, Robert Fettiplace, Ardem Patapoutian, Ulrich Müller
Auditory hair cells contain mechanotransduction channels that rapidly open in response to sound-induced vibrations. We report here that auditory hair cells contain two molecularly distinct mechanotransduction channels. One ion channel is activated by sound and is responsible for sensory transduction. This sensory transduction channel is expressed in hair cell stereocilia, and previous studies show that its activity is affected by mutations in the genes encoding the transmembrane proteins TMHS, TMIE, TMC1 and TMC2...
November 28, 2016: Nature Neuroscience
Andrea Delle Vedove, Markus Storbeck, Raoul Heller, Irmgard Hölker, Malavika Hebbar, Anju Shukla, Olafur Magnusson, Sebahattin Cirak, Katta M Girisha, Mary O'Driscoll, Bart Loeys, Brunhilde Wirth
We report ten individuals of four independent consanguineous families from Turkey, India, Libya, and Pakistan with a variable clinical phenotype that comprises arthrogryposis, spontaneously resolving respiratory insufficiency at birth, muscular atrophy predominantly of the distal lower limbs, scoliosis, and mild distal sensory involvement. Using whole-exome sequencing, SNPchip-based linkage analysis, DNA microarray, and Sanger sequencing, we identified three independent homozygous frameshift mutations and a homozygous deletion of two exons in PIEZO2 that segregated in all affected individuals of the respective family...
November 3, 2016: American Journal of Human Genetics
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
Franz Alisch, Alexander Weichert, Karim Kalache, Viola Paradiso, Ann Carolin Longardt, Christof Dame, Katrin Hoffmann, Denise Horn
Gordon syndrome or distal arthrogryposis type 3 is a rare autosomal dominant disorder characterized by contractures of upper and lower limbs. It is distinguishable from other forms of distal arthrogryposis by cleft palate and short stature. Recently, Gordon syndrome has been associated to heterozygous mutations in the piezo-type mechanosensitive ion channel component 2 gene (PIEZO2). Different mutations of this gene also cause distal arthrogryposis type 5 and Marden-Walker syndrome. Dysfunction of this ion channel provides pleiotropic effects on joints, ocular muscles, and bone development...
October 7, 2016: American Journal of Medical Genetics. Part A
Man-Kyo Chung, Jennifer Park, Jamila Asgar, Jin Y Ro
BACKGROUND: Chronic pain in masticatory muscles is a major medical problem. Although mechanisms underlying persistent pain in masticatory muscles are not fully understood, sensitization of nociceptive primary afferents following muscle inflammation or injury contributes to muscle hyperalgesia. It is well known that craniofacial muscle injury or inflammation induces regulation of multiple genes in trigeminal ganglia, which is associated with muscle hyperalgesia. However, overall transcriptional profiles within trigeminal ganglia following masseter inflammation have not yet been determined...
2016: Molecular Pain
A A Mahmud, N A Nahid, C Nassif, M S B Sayeed, M U Ahmed, M Parveen, M I Khalil, M M Islam, Z Nahar, F Rypens, F F Hamdan, G A Rouleau, A Hasnat, J L Michaud
Dominant mutations in PIEZO2, which codes for the principal mechanotransduction channel for proprioception and touch sensation, have been found to cause different forms of distal arthrogryposis. Some observations suggest that these dominant mutations induce a gain-of-function effect on the channel. Here, we report a consanguineous family with three siblings who showed short stature, scoliosis, gross motor impairment, and a progressive form of contractures involving the distal joints that is distinct from that found in patients with dominant mutations in PIEZO2...
September 8, 2016: Clinical Genetics
Fan Wang, Kaitlyn Knutson, Constanza Alcaino, David R Linden, Simon J Gibbons, Purna Kashyap, Madhusudan Grover, Richard Oeckler, Philip A Gottlieb, Hui Joyce Li, Andrew B Leiter, Gianrico Farrugia, Arthur Beyder
The enterochromaffin (EC) cell in GI epithelium is the source of nearly all systemic serotonin (5-hydroxytryptamine, 5-HT), which is an important neurotransmitter and endocrine, autocrine and paracrine hormone. The EC cell is a specialized mechanosensor, and it is well known that it releases 5-HT in response to mechanical forces. However, the EC cell mechanotransduction mechanism is unknown. The aim of this work was to determine whether Piezo2 is involved in EC cell mechanosensation. Piezo2 mRNA was expressed in human jejunum and mouse mucosa from all segments of small bowel...
July 9, 2016: Journal of Physiology
Pratibha Narayanan, Julia Sondermann, Tom Rouwette, Samir Karaca, Henning Urlaub, Mišo Mitkovski, David Gomez-Varela, Manuela Schmidt
The ability of somatosensory neurons to perceive mechanical stimuli relies on specialized mechanotransducing proteins and their molecular environment. Only recently has the identity of a major transducer of mechanical forces in vertebrates been revealed by the discovery of Piezo2. Further work has established its pivotal role for innocuous touch in mice. Therefore, Piezo2 offers a unique platform for the molecular investigation of somatosensory mechanosensation. We performed a mass spectrometry-based interactomics screen on native Piezo2 in somatosensory neurons of mouse dorsal root ganglia (DRG)...
August 5, 2016: Journal of Proteome Research
Hong Yang, Chang Liu, Rong-Mei Zhou, Jin Yao, Xiu-Miao Li, Yi Shen, Hong Cheng, Jun Yuan, Biao Yan, Qin Jiang
Angiogenesis is important for invasive tumor growth and metastasis. Its inhibition is a promising tactic for limiting tumor progression. Here, we showed that Piezo2 knockdown led to decreased glioma angiogenesis and reduced vascular hyperpermeability. Piezo2 was highly expressed in tumor endothelial cells, and its knockdown suppressed vascular leakage and tumor angiogenesis. In a retinal vasculature development assay, corneal angiogenesis assay and a modified Miles assay, Piezo2 knockdown obviously decreased angiogenesis and vascular hyperpermeability...
June 17, 2016: Oncotarget
Danny Florez-Paz, Kiran Kumar Bali, Rohini Kuner, Ana Gomis
Proprioceptors are responsible for the conscious sensation of limb position and movement, muscle tension or force, and balance. Recent evidence suggests that Piezo2 is a low threshold mechanosensory receptor in the peripheral nervous system, acting as a transducer for touch sensation and proprioception. Thus, we characterized proprioceptive neurons in the mesencephalic trigeminal nucleus that are involved in processing proprioceptive information from the face and oral cavity. This is a specific population of neurons that produce rapidly adapting mechanically-activated currents that are fully dependent on Piezo2...
2016: Scientific Reports
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
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
Zhanfeng Jia, Ryo Ikeda, Jennifer Ling, Viacheslav Viatchenko-Karpinski, Jianguo G Gu
The Piezo2 channel is a newly identified mammalian mechanical transducer that confers rapidly adapting mechanically activated (RA-MA) currents in primary afferent neurons. The Piezo2 channels sense rapid membrane displacement, but it is not clear whether they are sensitive to osmotic swelling, which slowly increases static plasma membrane tension (SPMT). Here, we show that SPMT exerts a profound impact on the mechanical sensitivity of RA-MA channels in primary afferent neurons. RA-MA currents are greatly enhanced, and the mechanical threshold was reduced in both primary afferent neurons of rat dorsal root ganglia (DRG) and HEK293 cells heterologously expressing Piezo2 when these cells undergo osmotic swelling to increase SPMT...
April 22, 2016: Journal of Biological Chemistry
Pooja Singhmar, XiaoJiao Huo, Niels Eijkelkamp, Susana Rojo Berciano, Faiza Baameur, Fang C Mei, Yingmin Zhu, Xiaodong Cheng, David Hawke, Federico Mayor, Cristina Murga, Cobi J Heijnen, Annemieke Kavelaars
cAMP signaling plays a key role in regulating pain sensitivity. Here, we uncover a previously unidentified molecular mechanism in which direct phosphorylation of the exchange protein directly activated by cAMP 1 (EPAC1) by G protein kinase 2 (GRK2) suppresses Epac1-to-Rap1 signaling, thereby inhibiting persistent inflammatory pain. Epac1(-/-) mice are protected against inflammatory hyperalgesia in the complete Freund's adjuvant (CFA) model. Moreover, the Epac-specific inhibitor ESI-09 inhibits established CFA-induced mechanical hyperalgesia without affecting normal mechanical sensitivity...
March 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
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
Seung-Hyun Woo, Viktor Lukacs, Joriene C de Nooij, Dasha Zaytseva, Connor R Criddle, Allain Francisco, Thomas M Jessell, Katherine A Wilkinson, Ardem Patapoutian
Proprioception, the perception of body and limb position, is mediated by proprioceptors, specialized mechanosensory neurons that convey information about the stretch and tension experienced by muscles, tendons, skin and joints. In mammals, the molecular identity of the stretch-sensitive channel that mediates proprioception is unknown. We found that the mechanically activated nonselective cation channel Piezo2 was expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs in mice...
December 2015: Nature Neuroscience
Yanmei Qi, Laura Andolfi, Flavia Frattini, Florian Mayer, Marco Lazzarino, Jing Hu
Sensing force is crucial to maintain the viability of all living cells. Despite its fundamental importance, how force is sensed at the molecular level remains largely unknown. Here we show that stomatin-like protein-3 (STOML3) controls membrane mechanics by binding cholesterol and thus facilitates force transfer and tunes the sensitivity of mechano-gated channels, including Piezo channels. STOML3 is detected in cholesterol-rich lipid rafts. In mouse sensory neurons, depletion of cholesterol and deficiency of STOML3 similarly and interdependently attenuate mechanosensitivity while modulating membrane mechanics...
2015: Nature Communications
Eric Honoré, Joana Raquel Martins, David Penton, Amanda Patel, Sophie Demolombe
Piezo1 and Piezo2 are critically required for nonselective cationic mechanosensitive channels in mammalian cells. Within the last 5 years, tremendous progress has been made in understanding the function of Piezo1/2 in embryonic development, physiology, and associated disease states. A recent breakthrough was the discovery of a chemical opener for Piezo1, indicating that mechanosensitive ion channels can be opened independently of mechanical stress. We will review these new exciting findings, which might pave the road for the identification of novel therapeutic strategies...
2015: Reviews of Physiology, Biochemistry and Pharmacology
Eyup Cinar, Sitong Zhou, James DeCourcey, Yixuan Wang, Richard E Waugh, Jiandi Wan
Piezo proteins (Piezo1 and Piezo2) are recently identified mechanically activated cation channels in eukaryotic cells and associated with physiological responses to touch, pressure, and stretch. In particular, human RBCs express Piezo1 on their membranes, and mutations of Piezo1 have been linked to hereditary xerocytosis. To date, however, physiological functions of Piezo1 on normal RBCs remain poorly understood. Here, we show that Piezo1 regulates mechanotransductive release of ATP from human RBCs by controlling the shear-induced calcium (Ca(2+)) influx...
September 22, 2015: Proceedings of the National Academy of Sciences of the United States of America
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