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https://www.readbyqxmd.com/read/29921656/inhibition-of-somatosensory-mechanotransduction-by-annexin-a6
#1
Ramin Raouf, Stéphane Lolignier, Jane E Sexton, Queensta Millet, Sonia Santana-Varela, Anna Biller, Alice M Fuller, Vanessa Pereira, Jyoti S Choudhary, Mark O Collins, Stephen E Moss, Richard Lewis, Julie Tordo, Els Henckaerts, Michael Linden, John N Wood
Mechanically activated, slowly adapting currents in sensory neurons have been linked to noxious mechanosensation. The conotoxin NMB-1 (noxious mechanosensation blocker-1) blocks such currents and inhibits mechanical pain. Using a biotinylated form of NMB-1 in mass spectrometry analysis, we identified 67 binding proteins in sensory neurons and a sensory neuron-derived cell line, of which the top candidate was annexin A6, a membrane-associated calcium-binding protein. Annexin A6-deficient mice showed increased sensitivity to mechanical stimuli...
June 19, 2018: Science Signaling
https://www.readbyqxmd.com/read/29888402/a-3d-magnetic-hyaluronic-acid-hydrogel-for-magnetomechanical-neuromodulation-of-primary-dorsal-root-ganglion-neurons
#2
Andy Tay, Ali Sohrabi, Kate Poole, Stephanie Seidlits, Dino Di Carlo
Neuromodulation tools are useful to decipher and modulate neural circuitries implicated in functions and diseases. Existing electrical and chemical tools cannot offer specific neural modulation while optogenetics has limitations for deep tissue interfaces, which might be overcome by miniaturized optoelectronic devices in the future. Here, a 3D magnetic hyaluronic hydrogel is described that offers noninvasive neuromodulation via magnetomechanical stimulation of primary dorsal root ganglion (DRG) neurons. The hydrogel shares similar biochemical and biophysical properties as the extracellular matrix of spinal cord, facilitating healthy growth of functional neurites and expression of excitatory and inhibitory ion channels...
June 10, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29795280/probing-the-gating-mechanism-of-the-mechanosensitive-channel-piezo1-with-the-small-molecule-yoda1
#3
Jerome J Lacroix, Wesley M Botello-Smith, Yun Luo
Piezo proteins are transmembrane ion channels which transduce many forms of mechanical stimuli into electrochemical signals. Their pore, formed by the assembly of three identical subunits, opens by an unknown mechanism. Here, to probe this mechanism, we investigate the interaction of Piezo1 with the small molecule agonist Yoda1. By engineering chimeras between mouse Piezo1 and its Yoda1-insensitive paralog Piezo2, we first identify a minimal protein region required for Yoda1 sensitivity. We next study the effect of Yoda1 on heterotrimeric Piezo1 channels harboring wild type subunits and Yoda1-insensitive mutant subunits...
May 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29755320/mechanically-gated-ion-channels-in-mammalian-hair-cells
#4
REVIEW
Xufeng Qiu, Ulrich Müller
Hair cells in the inner ear convert mechanical stimuli provided by sound waves and head movements into electrical signal. Several mechanically evoked ionic currents with different properties have been recorded in hair cells. The search for the proteins that form the underlying ion channels is still in progress. The mechanoelectrical transduction (MET) channel near the tips of stereociliary in hair cells, which is responsible for sensory transduction, has been studied most extensively. Several components of the sensory mechanotransduction machinery in stereocilia have been identified, including the multi-transmembrane proteins tetraspan membrane protein in hair cell stereocilia (TMHS)/LHFPL5, transmembrane inner ear (TMIE) and transmembrane channel-like proteins 1 and 2 (TMC1/2)...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29724954/piezo2-channel-merkel-cell-signaling-modulates-the-conversion-of-touch-to-itch
#5
Jing Feng, Jialie Luo, Pu Yang, Junhui Du, Brian S Kim, Hongzhen Hu
The somatosensory system relays many signals ranging from light touch to pain and itch. Touch is critical to spatial awareness and communication. However, in disease states, innocuous mechanical stimuli can provoke pathologic sensations such as mechanical itch (alloknesis). The molecular and cellular mechanisms that govern this conversion remain unknown. We found that in mice, alloknesis in aging and dry skin is associated with a loss of Merkel cells, the touch receptors in the skin. Targeted genetic deletion of Merkel cells and associated mechanosensitive Piezo2 channels in the skin was sufficient to produce alloknesis...
May 4, 2018: Science
https://www.readbyqxmd.com/read/29669276/tmem150c-tentonin3-is-a-regulator-of-mechano-gated-ion-channels
#6
Evan O Anderson, Eve R Schneider, Jon D Matson, Elena O Gracheva, Sviatoslav N Bagriantsev
Neuronal mechano-sensitivity relies on mechano-gated ion channels, but pathways regulating their activity remain poorly understood. TMEM150C was proposed to mediate mechano-activated current in proprioceptive neurons. Here, we studied functional interaction of TMEM150C with mechano-gated ion channels from different classes (Piezo2, Piezo1, and the potassium channel TREK-1) using two independent methods of mechanical stimulation. We found that TMEM150C significantly prolongs the duration of the mechano-current produced by all three channels, decreases apparent activation threshold in Piezo2, and induces persistent current in Piezo1...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29626181/disability-in-adults-with-arthrogryposis-is-severe-partly-invisible-and-varies-by-genotype
#7
Shenhao Dai, Klaus Dieterich, Marie Jaeger, Bernard Wuyam, Pierre-Simon Jouk, Dominic Pérennou
OBJECTIVE: To understand the disability of adults with arthrogryposis multiplex congenita (AMC), a rare disease spectrum characterized by at least 2 joint contractures at birth in different body areas. METHODS: This is a retrospective analysis of data for unselected persons with AMC referred to the French center for adults with AMC from 2010 to 2016. All underwent a pluriprofessional systematic and comprehensive investigation of deficits, activity limitation, and participation restriction according to the International Classification of Functioning, Disability and Health and genetic analysis when indicated...
May 1, 2018: Neurology
https://www.readbyqxmd.com/read/29521261/myotubularin-related-protein-2-and-its-phospholipid-substrate-pip-2-control-piezo2-mediated-mechanotransduction-in-peripheral-sensory-neurons
#8
Pratibha Narayanan, Meike Hütte, Galina Kudryasheva, Francisco J Taberner, Stefan G Lechner, Florian Rehfeldt, David Gomez-Varela, Manuela Schmidt
Piezo2 ion channels are critical determinants of the sense of light touch in vertebrates. Yet, their regulation is only incompletely understood. We recently identified myotubularin related protein-2 (Mtmr2), a phosphoinositide (PI) phosphatase, in the native Piezo2 interactome of murine dorsal root ganglia (DRG). Here, we demonstrate that Mtmr2 attenuates Piezo2-mediated rapidly adapting mechanically activated (RA-MA) currents. Interestingly, heterologous Piezo1 and other known MA current subtypes in DRG appeared largely unaffected by Mtmr2...
March 9, 2018: ELife
https://www.readbyqxmd.com/read/29471041/mechanically-activated-ion-channels
#9
Boris Martinac, Kate Poole
The ability of cells to sense and respond to their physical environment is fundamental to a broad spectrum of biological processes. Cells express an array of force sensors that can transduce mechanical inputs into biochemical signals, including the mechanically activated ion channels PIEZO1, PIEZO2 and TRPV4. The identification and characterisation of mechanically activated ion channels has proven challenging, as has identifying their mode of activation and regulation in vivo. However, the diverse channelopathies associated with the known channels highlights their physiological importance...
April 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29432180/piezo2-channel-regulates-rhoa-and-actin-cytoskeleton-to-promote-cell-mechanobiological-responses
#10
Carlos Pardo-Pastor, Fanny Rubio-Moscardo, Marina Vogel-González, Selma A Serra, Alexandros Afthinos, Sanela Mrkonjic, Olivier Destaing, Juan F Abenza, José M Fernández-Fernández, Xavier Trepat, Corinne Albiges-Rizo, Konstantinos Konstantopoulos, Miguel A Valverde
Actin polymerization and assembly into stress fibers (SFs) is central to many cellular processes. However, how SFs form in response to the mechanical interaction of cells with their environment is not fully understood. Here we have identified Piezo2 mechanosensitive cationic channel as a transducer of environmental physical cues into mechanobiological responses. Piezo2 is needed by brain metastatic cells from breast cancer (MDA-MB-231-BrM2) to probe their physical environment as they anchor and pull on their surroundings or when confronted with confined migration through narrow pores...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29374927/-advances-in-the-research-of-function-of-merkel-cells-in-tactile-formation-of-skin
#11
REVIEW
X You, Z R Wei
Skin is the largest sense organ of human, with many mechanoreceptor cells under epidermis or dermis of skin and Merkel cell is one of them. It has been confirmed that Merkel cells play an important role in the process of mechanical transmission of mammalian soft tactile stimulation. Researches showed that Merkel cells had close relation to tactile formation and functioned by Merkel cell-neurite complexes and ion channels Piezo2. This article reviews Merkel cells and the function, problem and prospect of Merkel cells in tactile formation...
January 20, 2018: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/29324706/endothelial-ca-2-signaling-and-the-resistance-to-anticancer-treatments-partners-in-crime
#12
REVIEW
Francesco Moccia
Intracellular Ca2+ signaling drives angiogenesis and vasculogenesis by stimulating proliferation, migration, and tube formation in both vascular endothelial cells and endothelial colony forming cells (ECFCs), which represent the only endothelial precursor truly belonging to the endothelial phenotype. In addition, local Ca2+ signals at the endoplasmic reticulum (ER)-mitochondria interface regulate endothelial cell fate by stimulating survival or apoptosis depending on the extent of the mitochondrial Ca2+ increase...
January 11, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29261642/structure-of-the-mechanically-activated-ion-channel-piezo1
#13
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. Piezo proteins are distinct from other ion channels and their structure remains poorly defined, which impedes 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-bladed propeller shape with a curved transmembrane region containing at least 26 transmembrane helices per protomer...
February 22, 2018: Nature
https://www.readbyqxmd.com/read/29241539/functional-and-molecular-characterization-of-mechanoinsensitive-silent-nociceptors
#14
Vincenzo Prato, Francisco J Taberner, James R F Hockley, Gerard Callejo, Alice Arcourt, Bassim Tazir, Leonie Hammer, Paulina Schad, Paul A Heppenstall, Ewan S Smith, Stefan G Lechner
Mechanical and thermal hyperalgesia (pain hypersensitivity) are cardinal signs of inflammation. Although the mechanism underlying thermal hyperalgesia is well understood, the cellular and molecular basis of mechanical hyperalgesia is poorly described. Here, we have identified a subset of peptidergic C-fiber nociceptors that are insensitive to noxious mechanical stimuli under normal conditions but become sensitized to such stimuli when exposed to the inflammatory mediator nerve growth factor (NGF). Strikingly, NGF did not affect mechanosensitivity of other nociceptors...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29228535/the-role-of-piezo2-in-human-mechanosensation
#15
Nima Rezaei, Amene Saghazadeh
No abstract text is available yet for this article.
October 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/29212024/cell-type-specific-splicing-of-piezo2-regulates-mechanotransduction
#16
Marcin Szczot, Leah A Pogorzala, Hans Jürgen Solinski, Lynn Young, Philina Yee, Claire E Le Pichon, Alexander T Chesler, Mark A Hoon
Piezo2 is a mechanically activated ion channel required for touch discrimination, vibration detection, and proprioception. Here, we discovered that Piezo2 is extensively spliced, producing different Piezo2 isoforms with distinct properties. Sensory neurons from both mice and humans express a large repertoire of Piezo2 variants, whereas non-neuronal tissues express predominantly a single isoform. Notably, even within sensory ganglia, we demonstrate the splicing of Piezo2 to be cell type specific. Biophysical characterization revealed substantial differences in ion permeability, sensitivity to calcium modulation, and inactivation kinetics among Piezo2 splice variants...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29171028/the-mechanosensitive-piezo1-channel-structural-features-and-molecular-bases-underlying-its-ion-permeation-and-mechanotransduction
#17
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...
March 15, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29162691/dabbling-with-piezo2-for-mechanosensation
#18
Ruhma Syeda
No abstract text is available yet for this article.
December 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29109250/molecular-basis-of-tactile-specialization-in-the-duck-bill
#19
Eve R Schneider, Evan O Anderson, Marco Mastrotto, Jon D Matson, Vincent P Schulz, Patrick G Gallagher, Robert H LaMotte, Elena O Gracheva, Sviatoslav N Bagriantsev
Tactile-foraging ducks are specialist birds known for their touch-dependent feeding behavior. They use dabbling, straining, and filtering to find edible matter in murky water, relying on the sense of touch in their bill. Here, we present the molecular characterization of embryonic duck bill, which we show contains a high density of mechanosensory corpuscles innervated by functional rapidly adapting trigeminal afferents. In contrast to chicken, a visually foraging bird, the majority of duck trigeminal neurons are mechanoreceptors that express the Piezo2 ion channel and produce slowly inactivating mechano-current before hatching...
December 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29030909/global-gene-expression-profiles-of-hematopoietic-stem-and-progenitor-cells-from-patients-with-chronic-myeloid-leukemia-the-effect-of-in-vitro-culture-with-or-without-imatinib
#20
Sócrates Avilés-Vázquez, Antonieta Chávez-González, Alfredo Hidalgo-Miranda, Dafne Moreno-Lorenzana, Lourdes Arriaga-Pizano, Miguel Á Sandoval-Esquivel, Manuel Ayala-Sánchez, Rafael Aguilar, Luis Alfaro-Ruiz, Hector Mayani
In this study, we determined the gene expression profiles of bone marrow-derived cell fractions, obtained from normal subjects and Chronic Myeloid Leukemia (CML) patients, that were highly enriched for hematopoietic stem (HSCs) and progenitor (HPCs) cells. Our results indicate that the profiles of CML HSCs and HPCs were closer to that of normal progenitors, whereas normal HSCs showed the most different expression profile of all. We found that the expression profiles of HSCs and HPCs from CML marrow were closer to each other than those of HSCs and HPCs from normal marrow...
December 2017: Cancer Medicine
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