scholarly journals Phospholipase D Transduces Force to TREK-1 Channels in a Biological Membrane

2019 ◽  
Author(s):  
E. Nicholas Petersen ◽  
Manasa Gudheti ◽  
Mahmud Arif Pavel ◽  
Keith R. Murphy ◽  
William W. Ja ◽  
...  
Keyword(s):  
Phospholipase D ◽  
Biological Membrane ◽  
Force Sensor ◽  
Chemical Signal ◽  
Downstream Effector ◽  
Phospholipase D2 ◽  
Mechanosensitive Ion Channel ◽  
Genetic Deletion ◽  
Living Organisms ◽  
Mechanical Transduction

AbstractThe transduction of force into a biological signal is critical to all living organisms. Recently, disruption of ordered lipids has emerged as an ‘atypical’ force sensor in biological membranes; however, disruption has yet to link with canonical channel mechanosensation. Here we show that forceinduced disruption and lipid mixing activates TWIK-related K+ channel (TREK-1), and that this activation is dependent on phospholipase D2 (PLD2). PLD2 transduces the force into a chemical signal phosphatidic acid (PA) that is then sensed by TREK-1 with a latency of <3 ms. TREK-1 then produces a mechanically induced change in membrane potential. Hence, in a biological membrane, we show the ordered lipid is the force sensor, PLD2 is a chemical transducer, and the ‘mechanosensitive’ ion channel TREK-1 is a downstream effector of mechanical transduction. Confirming this central role for PA singling in force transduction, genetic deletion of PLD decreases mechanosensitivity and pain thresholds in D. melanogaster.

Biology and Materials? Part II

MRS Bulletin ◽  
1992 ◽  
Vol 17 (11) ◽  
pp. 36-38 ◽  
Author(s):  
Mark Alper
Keyword(s):  
Brain Function ◽  
Chemical Structure ◽  
Biological Membrane ◽  
Large Fraction ◽  
The Other ◽  
Major Fraction ◽  
Membrane Structures ◽  
Protein Fibers ◽  
Complex Process ◽  
Living Organisms

The October issue of the MRS Bulletin focused on two areas of research in biomolecular materials; biomineralization and protein fibers. In addition, the development of a new carbohydrate-based material with a variety of novel properties was discussed.In this issue, we turn to two other types of materials based on biological systems: (1) polymers and other materials produced through enzyme-catalyzed biosynthetic reactions and (2) protein and lipid complexes based on biological membrane structures. In each case, as in the October issue, a discussion of how Nature produces and uses these materials is followed by reports describing manipulations of these systems to enhance their properties for nonbiological applications.In the October issue, Kaplan and Cappello discussed in detail the synthesis of proteins. They described how living organisms expend a very large fraction of their energy producing these polymers to grow and repair damage to their bodies. (The other major fraction of their energy is dedicated to maintenance of brain function). Synthesis of carbohydrates, lipids, and other materials, however, is achieved through a somewhat more complex process. The organism outlines a pathway that consists of a sequence of reactions; each reaction converts a substrate-the product of the preceding reaction-to a product which is the substrate for the next reaction. The net result of the action of the pathway is the conversion of a nutrient to a useful material, often of far different chemical structure.

scholarly journals Phospholipase D2 Mediates Acute Aldosterone Secretion in Response to Angiotensin II in Adrenal Glomerulosa Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2162-2170 ◽  
Author(s):  
Haixia Qin ◽  
Michael A. Frohman ◽  
Wendy B. Bollag
Keyword(s):  
Plasma Membrane ◽  
Angiotensin Ii ◽  
Cell Surface ◽  
Phosphatidic Acid ◽  
Phospholipase D ◽  
Cell Interior ◽  
Aldosterone Secretion ◽  
Phospholipase D2 ◽  
Glomerulosa Cells

In primary bovine adrenal glomerulosa cells, the signaling enzyme phospholipase D (PLD) is suggested to mediate priming, the enhancement of aldosterone secretion after pretreatment with and removal of angiotensin II (AngII), via the formation of persistently elevated diacylglycerol (DAG). To further explore PLD’s role in priming, glomerulosa cells were pretreated with an exogenous bacterial PLD. Using this approach, phosphatidic acid (PA) is generated on the outer, rather than the inner, leaflet of the plasma membrane. Although PA is not readily internalized, the PA is nonetheless rapidly hydrolyzed by cell-surface PA phosphatases to DAG, which efficiently flips to the inner leaflet and accesses the cell interior. Pretreatment with bacterial PLD resulted in priming upon subsequent AngII exposure, supporting a role of DAG in this process, because the increase in DAG persisted after exogenous PLD removal. To determine the PLD isoform mediating aldosterone secretion, and presumably priming, primary glomerulosa cells were infected with adenoviruses expressing GFP, PLD1, PLD2, or lipase-inactive mutants. Overexpressed PLD2 increased aldosterone secretion by approximately 3-fold over the GFP-infected control under basal conditions, with a significant enhancement to about 16-fold over the basal value upon AngII stimulation. PLD activity was also increased basally and upon stimulation with AngII. In contrast, PLD1 overexpression had little effect on aldosterone secretion, despite the fact that PLD activity was enhanced. In both cases, the lipase-inactive PLD mutants showed essentially no effect on PLD activity or aldosterone secretion. Our results suggest that PLD2 is the isoform that mediates aldosterone secretion and likely priming.

scholarly journals Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization

1997 ◽  
Vol 7 (3) ◽  
pp. 191-201 ◽  
Author(s):  
William C. Colley ◽  
Tsung-Chang Sung ◽  
Richard Roll ◽  
John Jenco ◽  
Scott M. Hammond ◽  
...  
Keyword(s):  
Phospholipase D ◽  
Cytoskeletal Reorganization ◽  
Phospholipase D2 ◽  
Regulatory Properties

scholarly journals Mechanosensitive Ion Channel Piezo1 Activated by Matrix Stiffness Regulates Oxidative Stress-Induced Senescence and Apoptosis in Human Intervertebral Disc Degeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-13 ◽  
Author(s):  
Bingjin Wang ◽  
Wencan Ke ◽  
Kun Wang ◽  
Gaocai Li ◽  
Liang Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Ion Channel ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Elasticity Modulus ◽  
Mechanosensitive Ion Channel ◽  
Mechanical Transduction ◽  
Crucial Part

Mechanical stimulation plays a crucial part in the development of intervertebral disc degeneration (IDD). Extracellular matrix (ECM) stiffness, which is a crucial mechanical microenvironment of the nucleus pulposus (NP) tissue, contributes to the pathogenesis of IDD. The mechanosensitive ion channel Piezo1 mediates mechanical transduction. This study purposed to investigate the function of Piezo1 in human NP cells under ECM stiffness. The expression of Piezo1 and the ECM elasticity modulus increased in degenerative NP tissues. Stiff ECM activated the Piezo1 channel and increased intracellular Ca2+ levels. Moreover, the activation of Piezo1 increased intracellular reactive oxygen species (ROS) levels and the expression of GRP78 and CHOP, which contribute to oxidative stress and endoplasmic reticulum (ER) stress. Furthermore, stiff ECM aggravated oxidative stress-induced senescence and apoptosis in human NP cells. Piezo1 inhibition alleviated oxidative stress-induced senescence and apoptosis, caused by the increase in ECM stiffness. Finally, Piezo1 silencing ameliorated IDD in an in vivo rat model and decreased the elasticity modulus of rat NP tissues. In conclusion, we identified the mechanosensitive ion channel Piezo1 in human NP cells as a mechanical transduction mediator for stiff ECM stimulation. Our results provide novel insights into the mechanism of mechanical transduction in NP cells, with potential for treating IDD.

The telomerase tale in vascular aging: regulation by estrogens and nitric oxide signaling

2009 ◽  
Vol 106 (1) ◽  
pp. 333-337 ◽  
Author(s):  
Antonella Farsetti ◽  
Annalisa Grasselli ◽  
Silvia Bacchetti ◽  
Carlo Gaetano ◽  
Maurizio C. Capogrossi
Keyword(s):  
Nitric Oxide ◽  
Estrogen Receptor Α ◽  
Cell Aging ◽  
Cross Point ◽  
Nitric Oxide Signaling ◽  
Downstream Effector ◽  
Relevant Risk Factor ◽  
Molecular Aspects ◽  
Living Organisms ◽  
Human Telomerase

Hormones and nitric oxide (NO), a free radical, are ancestral molecules, conserved through evolution, that modulate many aspects of the physiology and pathophysiology of living organisms by regulating transcription of genes involved in development, metabolism, and differentiation. Of interest, both estrogen and NO signaling, specifically through the estrogen receptor-α (ERα) and the endothelial isoform of the nitric oxide synthase (eNOS), have been shown to counteract endothelial senescence through a shared downstream effector, the catalytic subunit of human telomerase (hTERT), a key molecule in the aging process. Since aging is the first and most relevant risk factor in cardiovascular diseases, it is tempting to speculate that hTERT may be at the cross point between the NO and estrogen pathways. The present review will focus on the evolutionary and molecular aspects linking eNOS, ERs, and hTERT in counteracting the process of endothelial cell aging.

scholarly journals Phospholipase D and RalA Cooperate with the Epidermal Growth Factor Receptor To Transform 3Y1 Rat Fibroblasts

2000 ◽  
Vol 20 (2) ◽  
pp. 462-467 ◽  
Author(s):  
Zhimin Lu ◽  
Armand Hornia ◽  
Troy Joseph ◽  
Taiko Sukezane ◽  
Paul Frankel ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phospholipase D ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
Small Gtpase ◽  
Jun Kinase ◽  
Downstream Effector ◽  
Epidermal Growth ◽  
Rat Fibroblasts

ABSTRACT 3Y1 rat fibroblasts overexpressing the epidermal growth factor (EGF) receptor (EGFR cells) become transformed when treated with EGF. A common response to oncogenic and mitogenic stimuli is elevated phospholipase D (PLD) activity. RalA, a small GTPase that functions as a downstream effector molecule of Ras, exists in a complex with PLD1. In the EGFR cells, EGF induced a Ras-dependent activation of RalA. The activation of PLD by EGF in these cells was dependent upon both Ras and RalA. In contrast, EGF-induced activation of Erk1, Erk2, and Jun kinase was dependent on Ras but independent of RalA, indicating divergent pathways activated by EGF and mediated by Ras. The transformed phenotype induced by EGF in the EGFR cells was dependent upon both Ras and RalA. Importantly, overexpression of wild-type RalA or an activated RalA mutant increased PLD activity in the absence of EGF and transformed the EGFR cells. Although overexpression of PLD1 is generally toxic to cells, the EGFR cells not only tolerated PLD1 overexpression but also became transformed in the absence of EGF. These data demonstrate that either RalA or PLD1 can cooperate with EGF receptor to transform cells.

Regulation of Phospholipase D2:  Selective Inhibition of Mammalian Phospholipase D Isoenzymes by α- and β-Synucleins†

Biochemistry ◽  
1998 ◽  
Vol 37 (14) ◽  
pp. 4901-4909 ◽  
Author(s):  
John M. Jenco ◽  
Andrew Rawlingson ◽  
Brenda Daniels ◽  
Andrew J. Morris
Keyword(s):  
Phospholipase D ◽  
Selective Inhibition ◽  
Phospholipase D2

scholarly journals Organization and alternative splicing of the murine phospholipase D2 gene

1998 ◽  
Vol 331 (3) ◽  
pp. 845-851 ◽  
Author(s):  
Olga E. REDINA ◽  
Michael A. FROHMAN
Keyword(s):  
Signal Transduction ◽  
Alternative Splicing ◽  
Phospholipase D ◽  
Untranslated Region ◽  
Genomic Organization ◽  
Proximal Promoter ◽  
Promoter Sequences ◽  
Phospholipase D2 ◽  
Alternatively Spliced ◽  
Hydrolysis Of

Phospholipase D (PLD) catalyses the hydrolysis of phosphatidylcholine, generating phosphatidic acid and choline. Mammalian PLD activity derives from a family of membrane-associated enzymes that are activated by a wide variety of signal transduction events. cDNA species encoding human, mouse and rat PLD1 and PLD2 have recently been reported. In this study we undertook to determine the organization of the mouse PLD2 gene. We report that the gene spans 17.1 kb and contains 25 exons. Mouse PLD2 is notable for a relatively GC-rich and large 5´ untranslated region. Proximal promoter sequences upstream of the first exon contain several consensus SP1 sequences (GGGCGG) but lack TATA and CAAT boxes. Finally, alternatively spliced cDNA species identified for PLD1 and PLD2 are discussed in the context of the PLD2 genomic organization.

scholarly journals Src family kinases mediate neutrophil adhesion to adherent platelets

Blood ◽  
2006 ◽  
Vol 109 (6) ◽  
pp. 2461-2469 ◽  
Author(s):  
Virgilio Evangelista ◽  
Zehra Pamuklar ◽  
Antonio Piccoli ◽  
Stefano Manarini ◽  
Giuseppe Dell'Elba ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Src Family Kinases ◽  
Β2 Integrin ◽  
Contact Sites ◽  
Downstream Effector ◽  
Activated Platelets ◽  
Genetic Deletion ◽  
Src Family Tyrosine Kinases

Abstract Polymorphonuclear leukocyte (PMN)–platelet interactions at sites of vascular damage contribute to local and systemic inflammation. We sought to determine the role of “outside-in” signaling by Src-family tyrosine kinases (SFKs) in the regulation of αMβ2-integrin–dependent PMN recruitment by activated platelets under (patho)physiologic conditions. Activation-dependent epitopes in β2 integrin were exposed at the contact sites between PMNs and platelets and were abolished by SFK inhibitors. PMNs from αMβ2−/−, hck−/−fgr−/−, and hck−/−fgr−/−lyn−/− mice had an impaired capacity to adhere with activated platelets in suspension. Phosphorylation of Pyk2 accompanied PMN adhesion to platelets and was blocked by inhibition as well as by genetic deletion of αMβ2 integrin and SFKs. A Pyk2 inhibitor reduced platelet-PMN adhesion, indicating that Pyk2 may be a downstream effector of SFKs. Analysis of PMN-platelet interactions under flow revealed that SFK signaling was required for αMβ2-mediated shear-resistant adhesion of PMNs to adherent platelets, but was dispensable for P-selectin–PSGL-1–mediated recruitment and rolling. Finally, SFK activity was required to support PMN accumulation along adherent platelets at the site of vascular injury, in vivo. These results definitely establish a role for SFKs in PMN recruitment by activated platelets and suggest novel targets to disrupt the pathophysiologic consequences of platelet-leukocyte interactions in vascular disease.

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