Analysis of phosphorylation of the myosin-targeting subunit of myosin light chain phosphatase by Phos-tag SDS-PAGE
Phosphorylation of the myosin-targeting subunit 1 of myosin light chain phosphatase (MYPT1) plays an important role in the regulation of smooth muscle contraction, and several sites of phosphorylation by different protein Ser/Thr kinases have been identified. Furthermore, in some instances, phosphorylation at specific sites affects phosphorylation at neighboring sites, with functional consequences. Characterization of the complex phosphorylation of MYPT1 in tissue samples at rest and in response to contractile and relaxant stimuli is, therefore, challenging. We have exploited Phos-tag SDS-PAGE in combination with Western b...
Source: AJP: Cell Physiology - April 14, 2016 Category: Cytology Authors: Sutherland, C., MacDonald, J. A., Walsh, M. P. Tags: Cell Signaling: Proteins, Pathways and Mechanisms CALL FOR PAPERS Source Type: research
Leaky ryanodine receptors delay the activation of store overload-induced Ca2+ release, a mechanism underlying malignant hyperthermia-like events in dystrophic muscle
We present a hypothesis that SOICR activation is required in healthy muscle and that this mechanism works suboptimally in mdx fibers to fail to limit the activation of store-operated Ca2+ entry. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - April 14, 2016 Category: Cytology Authors: Cully, T. R., Launikonis, B. S. Tags: Cell Signaling: Proteins, Pathways and Mechanisms CALL FOR PAPERS Source Type: research
Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles
Receptor-activator of nuclear factor-B (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 con...
Source: AJP: Cell Physiology - April 14, 2016 Category: Cytology Authors: Dufresne, S. S., Dumont, N. A., Boulanger-Piette, A., Fajardo, V. A., Gamu, D., Kake-Guena, S.-A., David, R. O., Bouchard, P., Lavergne, E., Penninger, J. M., Pape, P. C., Tupling, A. R., Frenette, J. Tags: Cell Signaling: Proteins, Pathways and Mechanisms CALL FOR PAPERS Source Type: research
Molecular mechanisms of STIM/Orai communication
Ca2+ entry into the cell via store-operated Ca2+ release-activated Ca2+ (CRAC) channels triggers diverse signaling cascades that affect cellular processes like cell growth, gene regulation, secretion, and cell death. These store-operated Ca2+ channels open after depletion of intracellular Ca2+ stores, and their main features are fully reconstituted by the two molecular key players: the stromal interaction molecule (STIM) and Orai. STIM represents an endoplasmic reticulum-located Ca2+ sensor, while Orai forms a highly Ca2+-selective ion channel in the plasma membrane. Functional as well as mutagenesis studies together with ...
Source: AJP: Cell Physiology - April 14, 2016 Category: Cytology Authors: Derler, I., Jardin, I., Romanin, C. Tags: STIM and Orai Proteins in Calcium Signaling THEMES Source Type: research
Oxygen sensing by the carotid body: mechanisms and role in adaptation to hypoxia
Oxygen (O2) is fundamental for cell and whole-body homeostasis. Our understanding of the adaptive processes that take place in response to a lack of O2 (hypoxia) has progressed significantly in recent years. The carotid body (CB) is the main arterial chemoreceptor that mediates the acute cardiorespiratory reflexes (hyperventilation and sympathetic activation) triggered by hypoxia. The CB is composed of clusters of cells (glomeruli) in close contact with blood vessels and nerve fibers. Glomus cells, the O2-sensitive elements in the CB, are neuron-like cells that contain O2-sensitive K+ channels, which are inhibited by hypox...
Source: AJP: Cell Physiology - April 14, 2016 Category: Cytology Authors: Lopez-Barneo, J., Gonzalez-Rodriguez, P., Gao, L., Fernandez-Agüera, M. C., Pardal, R., Ortega-Saenz, P. Tags: Cellular Responses to Hypoxia THEMES Source Type: research
Pivotal role of AKAP121 in mitochondrial physiology
In this Perspective, we discuss some recent developments in the study of the mitochondrial scaffolding protein AKAP121 (also known as AKAP1, or AKAP149 as the human homolog), with an emphasis on its role in mitochondrial physiology. AKAP121 has been identified to function as a key regulatory molecule in several mitochondrial events including oxidative phosphorylation, the control of membrane potential, fission-induced apoptosis, maintenance of mitochondrial Ca2+ homeostasis, and the phosphorylation of various mitochondrial respiratory chain substrate molecules. Furthermore, we discuss the role of hypoxia in prompting cellu...
Source: AJP: Cell Physiology - April 14, 2016 Category: Cytology Authors: Czachor, A., Failla, A., Lockey, R., Kolliputi, N. Tags: PERSPECTIVES Source Type: research
Reply to "Letter to the editor: Titin-actin interaction: the report of its death was an exaggeration"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - March 31, 2016 Category: Cytology Authors: Rassier, D. E. Tags: LETTERS TO THE EDITOR Source Type: research
Letter to the editor: "Titin-actin interaction: the report of its death was an exaggeration"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - March 31, 2016 Category: Cytology Authors: Nishikawa, K. Tags: LETTERS TO THE EDITOR Source Type: research
A novel anti-inflammatory role of GPR120 in intestinal epithelial cells
GPR120 (free fatty acid receptor-4) is a G protein-coupled receptor for medium- and long-chain unsaturated fatty acids, including -3 fatty acids. Recent studies have shown GPR120 to play cardinal roles in metabolic disorders via modulation of gut hormone secretion and insulin sensitivity and to exert anti-inflammatory effects in macrophages and adipose tissues. However, information on anti-inflammatory role of GPR120 at the level of intestinal epithelium is very limited. Current studies demonstrated differential levels of GPR120 mRNA and protein along the length of the human, mouse, and rat intestine and delineated distinc...
Source: AJP: Cell Physiology - March 31, 2016 Category: Cytology Authors: Anbazhagan, A. N., Priyamvada, S., Gujral, T., Bhattacharyya, S., Alrefai, W. A., Dudeja, P. K., Borthakur, A. Tags: ARTICLES Source Type: research
Novel regulatory mechanism in human urinary bladder: central role of transient receptor potential melastatin 4 channels in detrusor smooth muscle function
In conclusion, TRPM4 channels regulate human DSM excitability and contractility and are critical determinants of human urinary bladder function. Thus, TRPM4 channels could represent promising novel targets for the pharmacological or genetic control of overactive bladder. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - March 31, 2016 Category: Cytology Authors: Hristov, K. L., Smith, A. C., Parajuli, S. P., Malysz, J., Rovner, E. S., Petkov, G. V. Tags: EDITORIAL FOCUS Source Type: research
New life in overactive bladder. Focus on "Novel regulatory mechanism in human urinary bladder: central role of transient receptor potential melastatin 4 channels in detrusor smooth muscle function"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - March 31, 2016 Category: Cytology Authors: Hamilton, K. L. Tags: EDITORIAL FOCUS Source Type: research
Hydrophobic motif site-phosphorylated protein kinase C{beta}II between mTORC2 and Akt regulates high glucose-induced mesangial cell hypertrophy
PKCβII controls the pathologic features of diabetic nephropathy, including glomerular mesangial cell hypertrophy. PKCβII contains the COOH-terminal hydrophobic motif site Ser-660. Whether this hydrophobic motif phosphorylation contributes to high glucose-induced mesangial cell hypertrophy has not been determined. Here we show that, in mesangial cells, high glucose increased phosphorylation of PKCβII at Ser-660 in a phosphatidylinositol 3-kinase (PI3-kinase)-dependent manner. Using siRNAs to downregulate PKCβII, dominant negative PKCβII, and PKCβII hydrophobic motif phosphorylation-deficient mu...
Source: AJP: Cell Physiology - March 31, 2016 Category: Cytology Authors: Das, F., Ghosh-Choudhury, N., Mariappan, M. M., Kasinath, B. S., Choudhury, G. G. Tags: Cell Signaling: Proteins, Pathways and Mechanisms CALL FOR PAPERS Source Type: research
Iodide excess regulates its own efflux: a possible involvement of pendrin
In conclusion, these data suggest that pendrin may have an important role in mediating iodide efflux in thyrocytes, especially under conditions of iodide excess. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - March 31, 2016 Category: Cytology Authors: Calil-Silveira, J., Serrano-Nascimento, C., Kopp, P. A., Nunes, M. T. Tags: Cell Signaling: Proteins, Pathways and Mechanisms CALL FOR PAPERS Source Type: research
Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation
Molecular chaperones that support protein quality control, including heat shock protein 70 (Hsp70), participate in diverse aspects of cellular and physiological function. Recent studies have reported roles for specific chaperone activities in blood platelets in maintaining hemostasis; however, the functions of Hsp70 in platelet physiology remain uninvestigated. Here we characterize roles for Hsp70 activity in platelet activation and function. In vitro biochemical, microscopy, flow cytometry, and aggregometry assays of platelet function, as well as ex vivo analyses of platelet aggregate formation in whole blood under shear,...
Source: AJP: Cell Physiology - March 31, 2016 Category: Cytology Authors: Rigg, R. A., Healy, L. D., Nowak, M. S., Mallet, J., Thierheimer, M. L. D., Pang, J., McCarty, O. J. T., Aslan, J. E. Tags: Cell Signaling: Proteins, Pathways and Mechanisms CALL FOR PAPERS Source Type: research
Altered expression of uncoupling protein 2 in GLP-1-producing cells after chronic high glucose exposure: implications for the pathogenesis of diabetes mellitus
Glucagon-like peptide-1 (GLP-1) is a gut L-cell hormone that enhances glucose-stimulated insulin secretion. Several approaches that prevent GLP-1 degradation or activate the GLP-1 receptor are being used to treat type 2 diabetes mellitus (T2DM) patients. In T2DM, GLP-1 secretion has been suggested to be impaired, and this defect appears to be a consequence rather than a cause of impaired glucose homeostasis. However, although defective GLP-1 secretion has been correlated with insulin resistance, little is known about the direct effects of chronic high glucose concentrations, which are typical in diabetes patients, on GLP-1...
Source: AJP: Cell Physiology - March 31, 2016 Category: Cytology Authors: Urbano, F., Filippello, A., Di Pino, A., Barbagallo, D., Di Mauro, S., Pappalardo, A., Rabuazzo, A. M., Purrello, M., Purrello, F., Piro, S. Tags: Cell Signaling: Proteins, Pathways and Mechanisms CALL FOR PAPERS Source Type: research
