Principles of c-di-GMP signalling in bacteria

Nature Reviews Microbiology, Journal Year: 2009, Volume and Issue: 7(4), P. 263 - 273

Published: March 16, 2009

Language: Английский

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A Coupled SYSTEM of Intracellular Ca ²⁺ Clocks and Surface Membrane Voltage Clocks Controls the Timekeeping Mechanism of the Heart’s Pacemaker

Circulation Research, Journal Year: 2010, Volume and Issue: 106(4), P. 659 - 673

Published: March 4, 2010

Abstract: Ion channels on the surface membrane of sinoatrial nodal pacemaker cells (SANCs) are proximal cause an action potential. Each individual channel type has been thoroughly characterized under voltage clamp, and ensemble ion currents reconstructed in silico generates rhythmic potentials. Thus, this can be envisioned as a “membrane clock” (M clock). Localized subsarcolemmal Ca 2+ releases generated by sarcoplasmic reticulum via ryanodine receptors during late diastolic depolarization referred to intracellular “Ca clock,” because their spontaneous occurrence is periodic clamp or detergent-permeabilized SANCs, well. In spontaneously firing M clocks do not operate isolation but work together numerous interactions modulated voltage, , protein kinase A CaMKII-dependent phosphorylation. Through these interactions, 2 subsystem become mutually entrained form robust, stable, coupled-clock system that drives normal cardiac cell automaticity. G protein–coupled signaling creates flexibility, ie, effects changes potential rate, impacting very same factors regulate robust basal function. This review examines evidence forms basis concept SANCs.

Language: Английский

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Caveolae as Organizers of Pharmacologically Relevant Signal Transduction Molecules

The Annual Review of Pharmacology and Toxicology, Journal Year: 2007, Volume and Issue: 48(1), P. 359 - 391

Published: Oct. 3, 2007

Caveolae, a subset of membrane (lipid) rafts, are flask-like invaginations the plasma that contain caveolin proteins, which serve as organizing centers for cellular signal transduction. Caveolins (-1, -2, and -3) have cytoplasmic N C termini, palmitolylation sites, scaffolding domain facilitates interaction organization signaling molecules so to help provide coordinated efficient Such components include upstream entities (e.g., G protein-coupled receptors (GPCRs), receptor tyrosine kinases, steroid hormone receptors) downstream heterotrimeric low-molecular-weight effector enzymes, ion channels). Diseases associated with aberrant may result in altered localization or expression proteins caveolae. Caveolin-knockout mice numerous abnormalities, some reflect impact total body knockout throughout life span. This review provides general overview caveolins caveolae, localize role caveolae/caveolin cardiac pulmonary pathophysiology, pharmacologic implications caveolar molecules, possibility caveolae might therapeutic target.

Language: Английский

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Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown

Trends in Biochemical Sciences, Journal Year: 2009, Volume and Issue: 35(2), P. 91 - 100

Published: Oct. 27, 2009

Language: Английский

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Physiological Roles for G Protein-Regulated Adenylyl Cyclase Isoforms: Insights from Knockout and Overexpression Studies

Neurosignals, Journal Year: 2008, Volume and Issue: 17(1), P. 5 - 22

Published: Oct. 27, 2008

Cyclic AMP is a universal second messenger, produced by family of adenylyl cyclase (AC) enzymes. The last three decades have brought wealth new information about the regulation cyclic production ACs. Nine hormone-sensitive, membrane-bound AC isoforms been identified in addition to tenth isoform that lacks membrane spans and more closely resembles cyanobacterial New model systems for purifying characterizing catalytic domains led crystal structure these mapping numerous interaction sites. However, big hurdles remain unraveling roles individual their physiological systems. In this review we explore latest on knockout overexpression studies better understand G protein ACs brain, olfactory bulb, heart.

Language: Английский

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Molecular Mechanism of Pancreatic and Salivary Gland Fluid and HCO₃⁻Secretion

Physiological Reviews, Journal Year: 2012, Volume and Issue: 92(1), P. 39 - 74

Published: Jan. 1, 2012

Fluid and HCO 3 − secretion is a vital function of all epithelia required for the survival tissue. Aberrant fluid associated with many epithelial diseases, such as cystic fibrosis, pancreatitis, Sjögren's syndrome, other inflammatory autoimmune diseases. Significant progress has been made over last 20 years in our understanding secretion, particular by secretory glands. glands two-step process. Acinar cells secrete isotonic which major salt NaCl. Subsequently, duct modifies volume electrolyte composition to absorb Cl . The relative secreted acinar modification fluids varies among meet their physiological functions. In pancreas, small amount NaCl-rich fluid, while absorbs secretes bulk pancreatic juice. appears be driven active secretion. salivary glands, saliva that contains high concentrations Na + both K this review, we focus on molecular mechanism pancreas highlight similarities fundamental mechanisms cell functions, point out differences gland-specific secretions.

Language: Английский

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Store-operated CRAC channels: function in health and disease

Nature Reviews Drug Discovery, Journal Year: 2010, Volume and Issue: 9(5), P. 399 - 410

Published: April 16, 2010

Language: Английский

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IP3 Receptors: Toward Understanding Their Activation

Cold Spring Harbor Perspectives in Biology, Journal Year: 2010, Volume and Issue: 2(12), P. a004010 - a004010

Published: Oct. 27, 2010

Colin W. Taylor and Stephen C. Tovey Department of Pharmacology, University Cambridge, Tennis Court Road, CB2 1PD, United Kingdom Correspondence: cwt1000{at}cam.ac.uk

Language: Английский

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Phase Separation of a PKA Regulatory Subunit Controls cAMP Compartmentation and Oncogenic Signaling

Cell, Journal Year: 2020, Volume and Issue: 182(6), P. 1531 - 1544.e15

Published: Aug. 25, 2020

Language: Английский

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The Prostanoid EP4 Receptor and Its Signaling Pathway

Pharmacological Reviews, Journal Year: 2013, Volume and Issue: 65(3), P. 1010 - 1052

Published: June 17, 2013

The EP4 prostanoid receptor is one of four subtypes for prostaglandin E₂. It belongs to the family G protein–coupled receptors. was originally identified, similar EP2 as a G_sα-coupled, adenylyl cyclase–stimulating receptor. signaling plays variety roles through cAMP effectors, i.e., protein kinase A and exchange activated by cAMP. However, emerging evidence from studies using pharmacological approaches genetically modified mice suggests that EP4, unlike EP2, can also be coupled G_iα, phosphatidylinositol 3-kinase, β-arrestin, or β-catenin. These pathways constitute unique widely distributed in body thus various physiologic pathophysiologic roles. In particular, closely related carcinogenesis, cardiac hypertrophy, vasodilation, vascular remodeling, bone gastrointestinal homeostasis, renal function, female reproductive function. addition classic anti-inflammatory action on mononuclear cells T cells, recent has shown contributes proinflammatory well. aim this review present current findings biologic functions we will discuss its diversity standpoint EP4-mediated signaling.

Language: Английский

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