Actins

Publication Title: 
PloS One

BACKGROUND: In a variety of organisms, including mammals, caloric restriction improves metabolic status and lowers the incidence of chronic-degenerative diseases, ultimately leading to increased lifespan. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that knockout mice for Eps8, a regulator of actin dynamics, display reduced body weight, partial resistance to age- or diet-induced obesity, and overall improved metabolic status. Alteration in the liver gene expression profile, in behavior and metabolism point to a calorie restriction-like phenotype in Eps8 knockout mice.

Author(s): 
Tocchetti, Arianna
Soppo, Charlotte Blanche Ekalle
Zani, Fabio
Bianchi, Fabrizio
Gagliani, Maria Cristina
Pozzi, Benedetta
Rozman, Jan
Elvert, Ralf
Ehrhardt, Nicole
Rathkolb, Birgit
Moerth, Corinna
Horsch, Marion
Fuchs, Helmut
Gailus-Durner, ValÈrie
Beckers, Johannes
Klingenspor, Martin
Wolf, Eckhard
HrabÈ de Angelis, Martin
Scanziani, Eugenio
Tacchetti, Carlo
Scita, Giorgio
Di Fiore, Pier Paolo
Offenh‰user, Nina
Publication Title: 
Annals of Neurology

The neuropathology of the primary dystonias is not well understood. We examined brains from identical twins with DYT1-negative, dopa-unresponsive dystonia. The twins exhibited mild developmental delays until age 12 years when they began developing rapidly progressive generalized dystonia. Genetic, metabolic, and imaging studies ruled out known causes of dystonia. Cognition was subnormal but stable until the last few years. Death occurred at ages 21 and 22 years. The brains were macroscopically unremarkable.

Author(s): 
Gearing, Marla
Juncos, Jorge L.
Procaccio, Vincent
Gutekunst, Claire-Anne
Marino-Rodriguez, Elaine M.
Gyure, Kymberly A.
Ono, Shoichiro
Santoianni, Robert
Krawiecki, Nicolas S.
Wallace, Douglas C.
Wainer, Bruce H.
Publication Title: 
The Journal of Biological Chemistry

Cell culture work suggests that signaling to polymerize cortical filamentous actin (F-actin) represents a required pathway for the optimal redistribution of the insulin-responsive glucose transporter, GLUT4, to the plasma membrane. Recent in vitro study further suggests that the actin-regulatory neural Wiskott-Aldrich syndrome protein (N-WASP) mediates the effect of insulin on the actin filament network. Here we tested whether similar cytoskeletal mechanics are essential for insulin-regulated glucose transport in isolated rat epitrochlearis skeletal muscle.

Author(s): 
Brozinick, Joseph T.
Hawkins, Eric D.
Strawbridge, Andrew B.
Elmendorf, Jeffrey S.
Publication Title: 
The Journal of Biological Chemistry

Muscle and fat cells develop insulin resistance when cultured under hyperinsulinemic conditions for sustained periods. Recent data indicate that early insulin signaling defects do not fully account for the loss of insulin action. Given that cortical filamentous actin (F-actin) represents an essential aspect of insulin regulated glucose transport, we tested to see whether cortical F-actin structure was compromised during chronic insulin treatment.

Author(s): 
Chen, Guoli
Raman, Priya
Bhonagiri, Padma
Strawbridge, Andrew B.
Pattar, Guruprasad R.
Elmendorf, Jeffrey S.
Publication Title: 
American Journal of Physiology. Cell Physiology

Cytoskeleton-dependent changes in cell shape are well-established factors regulating a wide range of cellular functions including signal transduction, gene expression, and matrix adhesion. Although the importance of mechanical forces on cell shape and function is well established in cultured cells, very little is known about these effects in whole tissues or in vivo. In this study we used ex vivo and in vivo models to investigate the effect of tissue stretch on mouse subcutaneous tissue fibroblast morphology.

Author(s): 
Langevin, Helene M.
Bouffard, Nicole A.
Badger, Gary J.
Iatridis, James C.
Howe, Alan K.
Publication Title: 
Clinical Cancer Research: An Official Journal of the American Association for Cancer Research

Alteration of actin polymerization and loss of actin filaments is a marker of cellular dedifferentiation and early malignant transformation. To study this phenomenon, an in vitro human urothelial model consisting of two cell lines, HUC-PC and MC-T11, were incorporated into the study design. These two cell lines have different malignant transformation potential. The effect of green tea extract (GTE), a potential anticancer agent, on actin remodeling was investigated.

Author(s): 
Lu, Qing-Yi
Jin, Yu-Sheng
Pantuck, Allan
Zhang, Zuo-Feng
Heber, David
Belldegrun, Arie
Brooks, Mai
Figlin, Robert
Rao, Jianyu
Publication Title: 
Diabetes

Phosphatidylinositol (PI) 4,5-bisphosphate (PIP(2)) plays a pivotal role in insulin-stimulated glucose transport as an important precursor to PI 3,4,5-trisphosphate (PIP(3)) and a key regulator of actin polymerization. Since endothelin (ET)-1 impairs insulin sensitivity and PIP(2) is a target of ET-1-induced signaling, we tested whether a change in insulin-stimulated PIP(3) generation and signaling, PIP(2)-regulated actin polymerization, or a combination of both accounted for ET-1-induced insulin resistance.

Author(s): 
Strawbridge, Andrew B.
Elmendorf, Jeffrey S.
Publication Title: 
Current Diabetes Reviews

The dissection of mechanisms that regulate glucose transport by insulin has revealed an intricate network of signaling molecules scattered from the insulin receptor to the intracellular glucose transporter GLUT4. It is also appreciated that some insulin receptor signals jaunt in different directions to regulate events essential for the efficient redistribution of GLUT4 to the plasma membrane. Moreover key assists in the process appear to be arranged by membrane lipids and cytoskeletal proteins.

Author(s): 
Brozinick, Joseph T.
Berkemeier, Bradley A.
Elmendorf, Jeffrey S.
Publication Title: 
Journal of Structural Biology

The cartilage is composed of chondrocytes embedded in a matrix of collagen fibrils interspersed within a network of proteoglycans and is constantly exposed to biomechanical forces during normal joint movement. Characterization of the surface morphology, cytoskeletal structure, adherance and elastic properties of these mechanosensitive cells are crucial in understanding the effects of mechanical forces around a cell and how a cell responds to changes in its physical environment.

Author(s): 
Iscru, Daniel F.
Anghelina, Mirela
Agarwal, Sudha
Agarwal, Gunjan
Publication Title: 
Endocrinology

We recently found that plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP(2))-regulated filamentous actin (F-actin) polymerization was diminished in hyperinsulinemic cell culture models of insulin resistance. Here we delineated whether increased glucose flux through the hexosamine biosynthesis pathway (HBP) causes the PIP(2)/F-actin dysregulation and insulin resistance induced by hyperinsulinemia.

Author(s): 
Bhonagiri, Padma
Pattar, Guruprasad R.
Horvath, Emily M.
Habegger, Kirk M.
McCarthy, Alicia M.
Elmendorf, Jeffrey S.

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