Amanda Buyan, Charles D Cox, Jonathan Barnoud, Jinyuan Li, Hannah S M Chan, Boris Martinac, Siewert J Marrink, Ben Corry
Touch, hearing, and blood pressure regulation require mechanically gated ion channels that convert mechanical stimuli into electrical currents. One such channel is Piezo1, which plays a key role in the transduction of mechanical stimuli in humans and is implicated in diseases, such as xerocytosis and lymphatic dysplasia. There is building evidence that suggests Piezo1 can be regulated by the membrane environment, with the activity of the channel determined by the local concentration of lipids, such as cholesterol and phosphoinositides...
September 2, 2020: Biophysical Journal
Pingping Wang, Yinjun Jia, Ting Liu, Yuh-Nung Jan, Wei Zhang
Animal feeding is controlled by external sensory cues and internal metabolic states. Does it also depend on enteric neurons that sense mechanical cues to signal fullness of the digestive tract? Here, we identify a group of piezo-expressing neurons innervating the Drosophila crop (the fly equivalent of the stomach) that monitor crop volume to avoid food overconsumption. These neurons reside in the pars intercerebralis (PI), a neuro-secretory center in the brain involved in homeostatic control, and express insulin-like peptides with well-established roles in regulating food intake and metabolism...
September 8, 2020: Neuron
Francesca Aglialoro, Naomi Hofsink, Menno Hofman, Nicole Brandhorst, Emile van den Akker
The non-selective mechanosensitive ion channel PIEZO1 controls erythrocyte volume homeostasis. Different missense gain-of-function mutations in PIEZO1 gene have been identified that cause Hereditary Xerocytosis (HX), a rare autosomal dominant haemolytic anemia. PIEZO1 expression is not limited to erythrocytes and expression levels are significantly higher in erythroid precursors, hinting to a role in erythropoiesis. During erythropoiesis, interactions between erythroblasts, central macrophages, and extracellular matrix within erythroblastic islands are important...
2020: Frontiers in Physiology
Mingqi Zhang, Xinghuan Ding, Qianqian Zhang, Jian Liu, Yisen Zhang, Ying Zhang, Zhongbin Tian, Wenqiang Li, Wei Zhu, Huibin Kang, Zhongxiao Wang, Xinzhi Wu, Chao Wang, Xinjian Yang, Kun Wang
BACKGROUND: Brain arteriovenous malformation (BAVM) is a main cause of cerebral hemorrhage and hemorrhagic stroke in adolescents. Morphologically, a BAVM is an abnormal connection between cerebrovascular arteries and veins. The genetic etiology of BAVMs has not been fully elucidated. In this study, we aim to investigate potential recessive genetic variants in BAVMs by interrogation of rare compound heterozygous variants. METHODS: We performed whole exome sequencing (WES) on 112 BAVM trios and analyzed the data for rare and deleterious compound heterozygous mutations associated with the disease...
August 26, 2020: Journal of Neurointerventional Surgery
Ting-Ting Liu, Xu-Fei Du, Bai-Bing Zhang, Hua-Xing Zi, Yong Yan, Jiang-An Yin, Han Hou, Shan-Ye Gu, Qi Chen, Jiu-Lin Du
During development, endothelial tip cells (ETCs) located at the leading edge of growing vascular plexus guide angiogenic sprouts to target vessels, and thus, ETC pathfinding is fundamental for vascular pattern formation in organs, including the brain. However, mechanisms of ETC pathfinding remain largely unknown. Here, we report that Piezo1-mediated Ca2+ activities at primary branches of ETCs regulate branch dynamics to accomplish ETC pathfinding during zebrafish brain vascular development. ETC branches display spontaneous local Ca2+ transients, and high- and low-frequency Ca2+ transients cause branch retraction through calpain and branch extension through nitric oxide synthase, respectively...
August 17, 2020: Neuron
Berk Aykut, Ruonan Chen, Jacqueline I Kim, Dongling Wu, Sorin A A Shadaloey, Raquel Abengozar, Pamela Preiss, Anjana Saxena, Smruti Pushalkar, Joshua Leinwand, Brian Diskin, Wei Wang, Gregor Werba, Matthew Berman, Steve Ki Buom Lee, Alireza Khodadadi-Jamayran, Deepak Saxena, William A Coetzee, George Miller
Piezo1 is a mechanosensitive ion channel that has gained recognition for its role in regulating diverse physiological processes. However, the influence of Piezo1 in inflammatory disease, including infection and tumor immunity, is not well studied. We postulated that Piezo1 links physical forces to immune regulation in myeloid cells. We found signal transduction via Piezo1 in myeloid cells and established this channel as the primary sensor of mechanical stress in these cells. Global inhibition of Piezo1 with a peptide inhibitor was protective against both cancer and septic shock and resulted in a diminution in suppressive myeloid cells...
August 21, 2020: Science Immunology
Yang Guo, Anna-Lena Merten, Ulrike Schöler, Ze-Yan Yu, Jasmina Cvetkovska, Diane Fatkin, Michael P Feneley, Boris Martinac, Oliver Friedrich
The transformation of electrical signals into mechanical action of the heart underlying blood circulation results in mechanical stimuli during active contraction or passive filling distention, which conversely modulate electrical signals. This feedback mechanism is known as cardiac mechano-electric coupling (MEC). The cardiac MEC involves complex activation of mechanical biosensors initiating short-term and long-term effects through Ca2+ signals in cardiomyocytes in acute and chronic pressure overload scenarios (e...
August 4, 2020: Progress in Biophysics and Molecular Biology
Juan D Matute, Jinzhi Duan, Richard S Blumberg
Serotonin production by enterochromaffin cells (ECs) is microbiota-dependent, but the mechanism of this is unknown. In this issue of Cell, Sugisawa et al. demonstrate that Piezo1 in ECs senses single-strand RNA (ssRNA) from intestinal microbiota to promote serotonin production. Deletion of Piezo1 in intestinal epithelium promotes bone formation, decreases peristalsis, and protects from colitis because of decreased serotonin.
August 6, 2020: Cell
Kathrin Diem, Michael Fauler, Giorgio Fois, Andreas Hellmann, Natalie Winokurow, Stefan Schumacher, Christine Kranz, Manfred Frick
Secretion of pulmonary surfactant in the alveoli of the lungs is essential to maintain lung function. Stretching of alveoli during lung inflation is the main trigger for surfactant secretion. Yet, the molecular mechanisms how mechanical distension of alveoli results in surfactant secretion are still elusive. The alveolar epithelium consists of alveolar epithelial type I (ATI) and surfactant secreting type II (ATII) cells. ATI, but not ATII cells, express caveolae, small plasma membrane invaginations that can respond to plasma membrane stresses and serve mechanotransductive roles...
August 3, 2020: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Daniele Zama, Giulia Giulietti, Edoardo Muratore, Immacolata Andolfo, Roberta Russo, Achille Iolascon, Andrea Pession
BACKGROUND: Dehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis is a rare, autosomal dominant hemolytic anemia characterized by macrocytosis, presence of stomatocytes and dehydration of red blood cells (RBCs). The dehydration is caused by a defect in cellular cation content. The most frequent expression of the pathology is hemolytic well-compensated anemia with high reticulocyte count, a tendency to macrocytosis, increased mean corpuscular hemoglobin concentration (MCHC) and mild jaundice...
July 23, 2020: Italian Journal of Pediatrics
S Qu, T Hu, O Qiu, Y Su, J Gu, Z Xia
BACKGROUND AND PURPOSE: Previous studies have suggested that increased mortality and disability in patients with brain tumor are associated with peritumoral brain edema. However, the mechanism of peritumoral brain edema in brain tumors is unknown. This study aimed to investigate the effect of Piezo1 overexpression on peritumoral brain edema in glioblastomas. MATERIALS AND METHODS: The Piezo1 expression in cell lines and paired samples was detected by quantitative reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry...
July 16, 2020: AJNR. American Journal of Neuroradiology
Chenghu Zhang, Ting Zhou, Zhipeng Chen, Meng Yan, Bochuan Li, Huizhen Lv, Chunjiong Wang, Song Xiang, Lei Shi, Yi Zhu, Ding Ai
Rationale: Atherosclerosis preferentially occurs at specific sites of the vasculature where endothelial cells (ECs) are exposed to disturbed blood flow. Translocation of integrin α5 to lipid rafts promotes integrin activation and ligation, which is critical for oscillatory shear stress (OSS)-induced EC activation. However, the underlying mechanism of OSS promoted integrin α5 lipid raft translocation has remained largely unknown. Objective: The objective of this study was to specify the mechanotransduction mechanism of OSS-induced integrin α5 translocation and subsequent EC activation...
July 16, 2020: Circulation Research
Ulisse Bocchero, Fabio Falleroni, Simone Mortal, Yunzhen Li, Dan Cojoc, Trevor Lamb, Vincent Torre
Photoreceptors are specialized cells devoted to the transduction of the incoming visual signals. Rods are able also to shed from their tip old disks and to synthesize at the base of the outer segment (OS) new disks. By combining electrophysiology, optical tweezers (OTs), and biochemistry, we investigate mechanosensitivity in the rods of Xenopus laevis, and we show that 1) mechanosensitive channels (MSCs), transient receptor potential canonical 1 (TRPC1), and Piezo1 are present in rod inner segments (ISs); 2) mechanical stimulation-of the order of 10 pN-applied briefly to either the OS or IS evokes calcium transients; 3) inhibition of MSCs decreases the duration of photoresponses to bright flashes; 4) bright flashes of light induce a rapid shortening of the OS; and 5) the genes encoding the TRPC family have an ancient association with the genes encoding families of protein involved in phototransduction...
July 15, 2020: PLoS Biology
Ben Short
JGP study shows that disruption of membrane cholesterol alters the organization and activity of mechanosensitive PIEZO1 channels.
August 3, 2020: Journal of General Physiology
Mauro Siragusa, Alberto Fernando Oliveira Justo, Pedro Felipe Malacarne, Anna Strano, Akshay Buch, Barbara Withers, Kevin G Peters, Ingrid Fleming
AIMS: Receptor-type vascular endothelial protein tyrosine phosphatase (VE-PTP) dephosphorylates Tie-2 as well as CD31, VE-cadherin and VEGFR2. The latter form a signal transduction complex that mediates the endothelial cell response to shear stress, including the activation of the endothelial nitric oxide (NO) synthase (eNOS). As VE-PTP expression is increased in diabetes, we investigated the consequences of VE-PTP inhibition (using AKB-9778) on blood pressure in diabetic patients and the role of VE-PTP in the regulation of eNOS activity and vascular reactivity...
July 11, 2020: Cardiovascular Research
Erika Sugisawa, Yasunori Takayama, Naoki Takemura, Takeshi Kondo, Shigetsugu Hatakeyama, Yutaro Kumagai, Masataka Sunagawa, Makoto Tominaga, Kenta Maruyama
Gastrointestinal enterochromaffin cells regulate bone and gut homeostasis via serotonin (5-hydroxytryptamine [5-HT]) production. A recent report suggested that gut microbes regulate 5-HT levels; however, the precise underlying molecular mechanisms are unexplored. Here, we reveal that the cation channel Piezo1 in the gut acts as a sensor of single-stranded RNA (ssRNA) governing 5-HT production. Intestinal epithelium-specific deletion of mouse Piezo1 profoundly disturbed gut peristalsis, impeded experimental colitis, and suppressed serum 5-HT levels...
June 29, 2020: Cell
An Song, Lin Lu, Yuxiu Li, Mei Lin, Xingxing Yuan, Xinqi Cheng, Weibo Xia, Ou Wang, Xiaoping Xing
Background: Diabetes is a global disease with rapidly increasing prevalence in the world. Glycated hemoglobin (HbA1c) as an important indicator of diabetes could reflect the average serum glucose level over 120 days. However, when using HbA1c to diagnose diabetes, it is important to consider other factors that may impact HbA1c level including age, race/ethnicity, detection method, and co-morbidities. Here we report a case of diabetes with normal hemoglobin but reduced HbA1c. Case report: A 57-year-old female patient was diagnosed with diabetes by oral glucose tolerance test results...
2020: Frontiers in Endocrinology
Ningfei Liu, Minzhe Gao, Ziyou Yu
OBJECTIVES: To explore the pathology underlying primary lymphedema. METHODS: Twenty-seven patients with unilateral congenital arm lymphedema who visited our clinic from 1 January 2014 to 30 May 2019 were enrolled. The patients' clinical signs, indocyanine green (ICG) lymphography, skin tissue immunohistochemical (IHC) staining, and whole-exome sequencing (WES) of tissue and blood were evaluated. RESULTS: Among the 27 patients, 18 and 9 were diagnosed with stage II and III lymphedema, respectively...
June 26, 2020: Journal of Vascular Surgery. Venous and Lymphatic Disorders
Pietro Ridone, Elvis Pandzic, Massimo Vassalli, Charles D Cox, Alexander Macmillan, Philip A Gottlieb, Boris Martinac
The human mechanosensitive ion channel PIEZO1 is gated by membrane tension and regulates essential biological processes such as vascular development and erythrocyte volume homeostasis. Currently, little is known about PIEZO1 plasma membrane localization and organization. Using a PIEZO1-GFP fusion protein, we investigated whether cholesterol enrichment or depletion by methyl-β-cyclodextrin (MBCD) and disruption of membrane cholesterol organization by dynasore affects PIEZO1-GFP's response to mechanical force...
August 3, 2020: Journal of General Physiology
Saša Svetina
The red blood cell (RBC) membrane contains a mechanosensitive cation channel Piezo1 that is involved in RBC volume homeostasis. In a recent model of the mechanism of its action it was proposed that Piezo1 cation permeability responds to changes of the RBC shape. The aim here is to review in a descriptive manner different previous studies of RBC behavior that formed the basis for this proposal. These studies include the interpretation of RBC and vesicle shapes based on the minimization of membrane bending energy, the analyses of various consequences of compositional and structural features of RBC membrane, in particular of its membrane skeleton and its integral membrane proteins, and the modeling of the establishment of RBC volume...
2020: Frontiers in Physiology
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