Cover image for Vol. 16 Issue 8

Edited By: Michael S. Marks, Trina A. Schroer, Tom H. Stevens, Sharon A. Tooze

Online ISSN: 1600-0854

Virtual Issue Muscle and Metabolism

Muscle and MetabolismVirtual Issue Muscle and Metabolism

Virtual issue cover legend: The pseudo-colored images obtained by immunofluorescent staining and confocal microscopy show the distribution of a protein called the Ryanodine Receptor (RyR) in dissociated mouse skeletal muscle fibers. Image courtesy of Stephane Vassilopoulos and Frances Brodsky.

TBC1D13 is a RAB35 Specific GAP that Plays an Important Role in GLUT4 Trafficking in Adipocytes
Jonathan R. Davey, Sean J. Humphrey, Jagath R. Junutula, Ashwini K. Mishra, David G. Lambright, David E. James and Jacqueline Stöckli
Traffic, Early View, Abstract
Insulin stimulates glucose transport in adipocytes by triggering translocation of GLUT4 glucose transporters to the plasma membrane (PM) and several Rabs including Rab10 have been implicated in this process. To delineate the molecular regulation of this pathway, we conducted a TBC/RabGAP overexpression screen in adipocytes. This identified TBC1D13 as a potent inhibitor of insulin-stimulated GLUT4 translocation without affecting other trafficking pathways...

Sarcolemmal Repair Is a Slow Process and Includes EHD2
Andreas Marg, Verena Schoewel, Tobias Timmel, Anne Schulze, Claudio Shah, Oliver Daumke, Simone Spuler
Traffic, Early View, Abstract
Skeletal muscle is continually subjected to microinjuries that must be repaired to maintain structure and function. Fluorescent dye influx after laser injury of muscle fibers is a commonly used assay to study membrane repair. This approach reveals that initial resealing only takes a few seconds. However, by this method the process of membrane repair can only be studied in part and is therefore poorly understood. We investigated...

A Centronuclear Myopathy – Dynamin 2 Mutation Impairs Autophagy in Mice
Anne-Cécile Durieux, Stéphane Vassilopoulos, Jeanne Lainé, Bodvaël Fraysse, Laura Briñas, Bernard Prudhon, Josiane Castells, Damien Freyssenet, Gisèle Bonne, Pascale Guicheney and Marc Bitoun
Traffic, Volume 13, Issue 6: 869–879, Abstract
Dynamin 2 (Dnm2) is involved in endocytosis and intracellular membrane trafficking through its function in vesicle formation from distinct membrane compartments. Heterozygous (HTZ) mutations in the DNM2 gene cause dominant centronuclear myopathy or Charcot–Marie–Tooth neuropathy. We generated a knock-in Dnm2R465W mouse model expressing the most frequent human ...

SNARE Proteins Underpin Insulin-Regulated GLUT4 Traffic
Nia J. Bryant and Gwyn W. Gould
Traffic, Volume 12, Issue 6: 657–664, Abstract
Delivery of the glucose transporter type 4 (GLUT4) from an intracellular location to the cell surface in response to insulin represents a specialized form of membrane traffic, known to be impaired in the disease states of insulin resistance and type 2 diabetes. Like all membrane trafficking events, this translocation of GLUT4 requires members of the SNARE family of proteins. Here, we discuss two ...

The Sugar Is sIRVed: Sorting Glut4 and Its Fellow Travelers
Konstantin V. Kandror and Paul F. Pilch
Traffic, Volume 12, Issue 6: 665–671, Abstract
Translocation of Glut4 to the plasma membrane of fat and skeletal muscle cells is mediated by specialized insulin-responsive vesicles (IRVs), whose protein composition consists primarily of glucose transporter isoform 4 (Glut4), insulin-responsive amino peptidase (IRAP), sortilin, lipoprotein receptor-related protein 1 (LRP1) and v-SNAREs. How can these proteins find each other in the ...

Mapping Insulin/GLUT4 Circuitry
Alexander F. Rowland, Daniel J. Fazakerley and David E. James
Traffic, Volume 12, Issue 6: 672–681, Abstract
One of the most important metabolic actions of insulin is catalysing glucose uptake into skeletal muscle and adipose tissue. This is accomplished via activation of the phosphatidylinositol-3-kinase/Akt signalling pathway and subsequent translocation of GLUT4 from intracellular storage vesicles to the plasma membrane. As such, this represents an ideal system for studying the convergence of ...

Insulin-Regulated Trafficking of GLUT4 Requires Ubiquitination
Christopher A. Lamb, Rebecca K. McCann, Jacqueline Stöckli, David E. James and Nia J. Bryant
Traffic, Volume 11, Issue 11, p. 1445–1454, Abstract
A major consequence of insulin binding its receptor on fat and muscle cells is translocation of the facilitative glucose transporter GLUT4 from an intracellular store to the cell surface where it serves to clear glucose from the bloodstream. Sorting of GLUT4 into its insulin-sensitive store requires the GGA [Golgi-localized, -ear-containing, ADP ribosylation factor (ARF)-binding] adaptor proteins...

Membrane Traffic and Muscle: Lessons from Human Disease
James J. Dowling, Elizabeth M. Gibbs, Eva L. Feldman
Traffic, Volume 9 Issue 7: 1035 - 1043, Abstract
Like all mammalian tissues, skeletal muscle is dependent on membrane traffic for proper development and homeostasis. This fact is underscored by the observation that several human diseases of the skeletal muscle are caused by mutations in gene products of the membrane trafficking machinery. An examination of these diseases and the proteins that underlie them is ...

The Sarcoplasmic Reticulum: An Organized Patchwork of Specialized Domains
Daniela Rossi, Virginia Barone, Emiliana Giacomello, Vincenza Cusimano, Vincenzo Sorrentino
Traffic, Volume 9 Issue 7: 1044 - 1049, Abstract
The sarcoplasmic reticulum (SR) of skeletal muscle cells is a convoluted structure composed of a variety of tubules and cisternae, which share a continuous lumen delimited by a single continuous membrane, branching to form a network that surrounds each myofibril. In this network, some specific domains basically represented by the longitudinal SR and the junctional SR can ...

Myoblast Fusion in Fly and Vertebrates: New Genes, New Processes and New Perspectives
Brian E. Richardson, Scott J. Nowak, Mary K. Baylies
Traffic, Volume 9 Issue 7: 1050 - 1059, Abstract
Muscle formation and repair depends critically on the fusion of myoblasts. Despite the importance of this process, little is known about the cellular and molecular mechanisms regulating fusion. Forward genetic screens in Drosophila melanogaster have uncovered genes that, when mutated, prevent myoblast fusion. Analyses of these gene products have indicated that the actin ...

Clathrin-Dependent and Independent Endocytosis of Glucose Transporter 4 (GLUT4) in Myoblasts: Regulation by Mitochondrial Uncoupling
Costin N. Antonescu, Mònica Díaz, Guiseppe Femia, Josep V. Planas, Amira Klip
Traffic, Volume 9 Issue 7: 1173 - 1190, Abstract
n myocytes and adipocytes, insulin increases glucose transporter 4 (GLUT4) exocytosis by promoting GLUT4 vesicle docking/fusion with the membrane. Less is known about the mechanism and regulation of GLUT4 endocytosis, particularly in myocytes. Here, we show that GLUT4 internalization in L6 myoblasts was inhibited in part by hypertonicity or clathrin heavy chain knockdown and ...

Similar [DE]XXXL[LI] Motifs Differentially Target GLUT8 and GLUT12 in Chinese Hamster Ovary Cells
Lauren B. Flessner, Kelle H. Moley
Traffic, Volume 10 Issue 3: 324 - 333, Abstract
The transport of glucose across cell membranes is mediated by facilitative glucose transporters (GLUTs). The recently identified class III GLUT12 is predominantly expressed in insulin-sensitive tissues such as heart, fat and skeletal muscle. We examined the subcellular localization of GLUT12 in Chinese hamster ovary and human embryonic kidney 293 cells stably expressing murine ...

Membrane Traffic in Skeletal Muscle
Mhairi C. Towler, Stephen J. Kaufman, Frances M. Brodsky
Traffic, Volume 5 Issue 3: 129 - 139, Abstract
Skeletal muscle tissue is made up of highly organized multinuclear cells. The internal organization of the muscle cell is dictated by the necessary regular arrangement of repeated units within the protein myofibrils that mediate muscle contraction. Skeletal muscle cells have the usual membrane traffic pathways for partitioning newly synthesized proteins, internalizing cell surface ...

Insulin Stimulates the Entry of GLUT4 into the Endosomal Recycling Pathway by a Quantal Mechanism
Adelle C. F. Coster, Roland Govers, David E. James
Traffic, Volume 5 Issue 10: 763 - 771, Abstract
The insulin-sensitive glucose transporter GLUT4 mediates the uptake of glucose into adipocytes and muscle cells. In this study we have used a novel 96-well plate fluorescence assay to study the kinetics of GLUT4 trafficking in 3T3-L1 adipocytes. We have found evidence for a graded release mechanism whereby GLUT4 is released into the plasma membrane recycling system in a ...

Munc 18-1 and Granuphilin Collaborate During Insulin Granule Exocytosis
Alejandra Tomas, Paolo Meda, Romano Regazzi, Jeffrey E. Pessin, Philippe A. Halban
Traffic, Volume 9 Issue 5: 813 - 832, Abstract
Munc 18-1 is a member of the Sec/Munc family of syntaxin-binding proteins known to bind to the plasma membrane Q-SNARE syntaxin1 and whose precise role in regulated exocytosis remains controversial. Here, we show that Munc 18-1 plays a positive role in regulated insulin secretion from pancreatic beta cells. Munc 18-1 depletion caused a loss in the secretory capacity of both ...

Cytoplasmic Targeting of Mutant Poly(A)-Binding Protein Nuclear 1 Suppresses Protein Aggregation and Toxicity in Oculopharyngeal Muscular Dystrophy
Aida Abu-Baker, Simon Laganiere, Xueping Fan, Janet Laganiere, Bernard Brais, Guy A. Rouleau
Traffic, Volume 6 Issue 9: 766 - 779, Abstract
Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by progressive eyelid drooping, swallowing difficulties and proximal limb weakness. The autosomal dominant form of this disease is caused by a polyalanine expansion from 10 to 12–17 residues, located at the N-terminus of the poly(A)-binding protein nuclear 1 (PABPN1). A distinct pathological ...

a-Sarcoglycan is Recycled from the Plasma Membrane in the Absence of Sarcoglycan Complex Assembly
Romesh A. Draviam, Bing Wang, Stuart H. Shand, Xiao Xiao, Simon C. Watkins
Traffic, Volume 7 Issue 7: 793 - 810, Abstract
The sarcoglycan complex consists of four subunits in skeletal muscle (a, ß, ?, and d-SG). Mutations in a-sarcoglycan (a-SG) result in the most common form of limb girdle muscular dystrophy. However, the function of a-SG remains unknown. In this report we attempt to clarify its function by delineating the trafficking pathway of a-SG in live cells. We present evidence, utilizing total ...

Insulin-Regulated Aminopeptidase Marks an Antigen-Stimulated Recycling Compartment in Mast Cells
Haini Liao, Susanna R. Keller, J. David Castle
Traffic, Volume 7 Issue 2: 155 - 167, Abstract
Insulin-regulated aminopeptidase (IRAP) is a marker for insulin-sensitive recycling compartments of fat and muscle cells that contain the glucose transporter isoform GLUT4. Unlike GLUT4, IRAP is expressed in many other cell types. Thus, it is a potential marker for regulated recycling compartments that are analogous to GLUT4 vesicles. In bone marrow-derived mast cells, IRAP is highly ...

Myotubularin Lipid Phosphatase Binds the hVPS15/hVPS34 Lipid Kinase Complex on Endosomes
Canhong Cao, Jocelyn Laporte, Jonathan M. Backer, Angela Wandinger-Ness, Mary-Pat Stein
Traffic, Volume 8 Issue 8: 1052 - 1067, Abstract
Myotubularins constitute a ubiquitous family of phosphatidylinositol (PI) 3-phosphatases implicated in several neuromuscular disorders. Myotubularin [myotubular myopathy 1 (MTM1)] PI 3-phosphatase is shown associated with early and late endosomes. Loss of endosomal phosphatidylinositol 3-phosphate [PI(3)P] upon overexpression of wild-type MTM1, but not a phosphatase- ...

Dysferlin in Membrane Trafficking and Patch Repair
Louise Glover, Robert H. Brown Jr
Traffic, Volume 8 Issue 7: 785 - 794, Abstract
The muscular dystrophies are a heterogeneous group of inherited disorders, defined by progressive muscle weakness and atrophy. Following the discovery of dystrophin, remarkable progress has been made in defining the molecular properties of proteins involved in the various dystrophies. This has underlined the importance of the dystrophin-associated protein complex as a cell ...

Golgi Complex Organization in Skeletal Muscle: A Role for Golgi-Mediated Glycosylation in Muscular Dystrophies?
Justin M. Percival, Stanley C. Froehner
Traffic, Volume 8 Issue 3: 184 - 194, Abstract
The Golgi complex (GC) is the central organelle of the classical secretory pathway, and it receives, modifies and packages proteins and lipids en route to their intracellular or extracellular destinations. Recent studies of congenital muscular dystrophies in skeletal muscle suggest an exciting new role for an old and well-established function of the GC: glycosylation. Glycosylation is ...

Processing and Assembly of the Dystrophin Glycoprotein Complex
Michael J. Allikian, Elizabeth M. McNally
Traffic, Volume 8 Issue 3: 177 - 183, Abstract
The assembly, processing and translocation of proteins occur constantly in all cells, and these processes also take place during the genesis, maintenance and repair of skeletal muscle. Skeletal muscle fibers are composed of myofibrils and are surrounded by a muscle plasma membrane, the sarcolemma. The sarcolemma serves as a docking location for many proteins. These proteins ...

rAAV6-Microdystrophin Rescues Aberrant Golgi Complex Organization in mdx Skeletal Muscles
Justin M. Percival, Paul Gregorevic, Guy L. Odom, Glen B. Banks, Jeffrey S. Chamberlain, Stanley C. Froehner
Traffic, Volume 8 Issue 10: 1424 - 1439, Abstract
Muscular dystrophies are a diverse group of severe degenerative muscle diseases. Recent interest in the role of the Golgi complex (GC) in muscle disease has been piqued by findings that several dystrophies result from mutations in putative Golgi-resident glycosyltransferases. Given this new role of the Golgi in sarcolemmal stability, we hypothesized that abnormal Golgi ...

Patients with a Non-dysferlin Miyoshi Myopathy have a Novel Membrane Repair Defect
Jyoti K. Jaiswal, Gareth Marlow, Gillian Summerill, Ibrahim Mahjneh, Sebastian Mueller, Maria Hill, Katsuya Miyake, Hannelore Haase, Louise V. B. Anderson, Isabelle Richard, Sari Kiuru-Enari, Paul L. McNeil, Sanford M. Simon, Rumaisa Bashir
Traffic, Volume 8 Issue 1: 77 - 88, Abstract
Two autosomal recessive muscle diseases, limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM), are caused by mutations in the dysferlin gene. These mutations result in poor ability to repair cell membrane damage, which is suggested to be the cause for this disease. However, many patients who share clinical features with MM-type muscular dystrophy do not ...

Insulin-Regulated Aminopeptidase Marks an Antigen-Stimulated Recycling Compartment in Mast Cells
Haini Liao, Susanna R. Keller, J. David Castle
Traffic, Volume 7 Issue 2: 155 - 167, Abstract
Insulin-regulated aminopeptidase (IRAP) is a marker for insulin-sensitive recycling compartments of fat and muscle cells that contain the glucose transporter isoform GLUT4. Unlike GLUT4, IRAP is expressed in many other cell types. Thus, it is a potential marker for regulated recycling compartments that are analogous to GLUT4 vesicles. In bone marrow-derived mast cells, IRAP is highly ...