scholarly journals Regulation of myonuclear positioning and muscle function by the skeletal muscle-specific CIP protein

2020 ◽  
Vol 117 (32) ◽  
pp. 19254-19265
Author(s):  
Jianming Liu ◽  
Zhan-Peng Huang ◽  
Mao Nie ◽  
Gang Wang ◽  
William J. Silva ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Neuromuscular Junctions ◽  
Linc Complex ◽  
Muscle Dystrophy ◽  
Microtubule Organizing Center ◽  
Anchoring Protein ◽  
Organizing Center ◽  
Genetic Deletion

The appropriate arrangement of myonuclei within skeletal muscle myofibers is of critical importance for normal muscle function, and improper myonuclear localization has been linked to a variety of skeletal muscle diseases, such as centronuclear myopathy and muscular dystrophies. However, the molecules that govern myonuclear positioning remain elusive. Here, we report that skeletal muscle-specific CIP (sk-CIP) is a regulator of nuclear positioning. Genetic deletion of sk-CIP in mice results in misalignment of myonuclei along the myofibers and at specialized structures such as neuromuscular junctions (NMJs) and myotendinous junctions (MTJs) in vivo, impairing myonuclear positioning after muscle regeneration, leading to severe muscle dystrophy inmdxmice, a mouse model of Duchenne muscular dystrophy. sk-CIP is localized to the centrosome in myoblasts and relocates to the outer nuclear envelope in myotubes upon differentiation. Mechanistically, we found that sk-CIP interacts with the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex and the centriole Microtubule Organizing Center (MTOC) proteins to coordinately modulate myonuclear positioning and alignment. These findings indicate that sk-CIP may function as a muscle-specific anchoring protein to regulate nuclear position in multinucleated muscle cells.

scholarly journals Mobility, Microtubule Nucleation and Structure of Microtubule-organizing Centers in Multinucleated Hyphae ofAshbya gossypii

2010 ◽  
Vol 21 (1) ◽  
pp. 18-28 ◽  
Author(s):  
Claudia Lang ◽  
Sandrine Grava ◽  
Tineke van den Hoorn ◽  
Rhonda Trimble ◽  
Peter Philippsen ◽  
...  
Keyword(s):  
Spindle Pole Body ◽  
Hyphal Growth ◽  
Spindle Pole ◽  
Microtubule Organizing Center ◽  
Microtubule Nucleation ◽  
Cytoplasmic Microtubule ◽  
Organizing Center ◽  
Cytoplasmic Side ◽  
Independent Mode

We investigated the migration of multiple nuclei in hyphae of the filamentous fungus Ashbya gossypii. Three types of cytoplasmic microtubule (cMT)-dependent nuclear movements were characterized using live cell imaging: short-range oscillations (up to 4.5 μm/min), rotations (up to 180° in 30 s), and long-range nuclear bypassing (up to 9 μm/min). These movements were superimposed on a cMT-independent mode of nuclear migration, cotransport with the cytoplasmic stream. This latter mode is sufficient to support wild-type-like hyphal growth speeds. cMT-dependent nuclear movements were led by a nuclear-associated microtubule-organizing center, the spindle pole body (SPB), which is the sole site of microtubule nucleation in A. gossypii. Analysis of A. gossypii SPBs by electron microscopy revealed an overall laminar structure similar to the budding yeast SPB but with distinct differences at the cytoplasmic side. Up to six perpendicular and tangential cMTs emanated from a more spherical outer plaque. The perpendicular and tangential cMTs most likely correspond to short, often cortex-associated cMTs and to long, hyphal growth-axis–oriented cMTs, respectively, seen by in vivo imaging. Each SPB nucleates its own array of cMTs, and the lack of overlapping cMT arrays between neighboring nuclei explains the autonomous nuclear oscillations and bypassing observed in A. gossypii hyphae.

Effects of In Vivo Doxorubicin Treatment on Skeletal Muscle Function

2011 ◽  
Vol 43 (Suppl 1) ◽  
pp. 903
Author(s):  
David S. Hydock ◽  
Chia-Ying Lien ◽  
Brock T. Jensen ◽  
Traci L. Parry ◽  
Carole M. Schneider ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Skeletal Muscle Function ◽  
Doxorubicin Treatment

Imaging of plasmacytoid dendritic cell interactions with T cells

Blood ◽  
2009 ◽  
Vol 113 (1) ◽  
pp. 75-84 ◽  
Author(s):  
María Mittelbrunn ◽  
Gloria Martínez del Hoyo ◽  
María López-Bravo ◽  
Noa B. Martín-Cofreces ◽  
Alix Scholer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Time Lapse ◽  
Cell Interactions ◽  
Type I ◽  
Microtubule Organizing Center ◽  
Immune Synapse ◽  
Organizing Center

Abstract Plasmacytoid dendritic cells (pDCs) efficiently produce type I interferon and participate in adaptive immune responses, although the molecular interactions between pDCs and antigen-specific T cells remain unknown. This study examines immune synapse (IS) formation between murine pDCs and CD4+ T cells. Mature pDCs formed canonical ISs, involving relocation to the contact site of the microtubule-organizing center, F-actin, protein kinase C-θ, and pVav, and activation of early signaling molecules in T cells. However, immature pDCs were less efficient at forming conjugates with T cells and inducing IS formation, microtubule-organizing center translocation, and T-cell signaling and activation. Time-lapse videomicroscopy and 2-photon in vivo imaging of pDC–T-cell interactions revealed that immature pDCs preferentially mediated transient interactions, whereas mature pDCs promoted more stable contacts. Our data indicate that, under steady-state conditions, pDCs preferentially establish transient contacts with naive T cells and show a very modest immunogenic capability, whereas on maturation, pDCs are able to form long-lived contacts with T cells and significantly enhance their capacity to activate these lymphocytes.

scholarly journals Muscle-Derived Extracellular Signal-Regulated Kinases 1 and 2 Are Required for the Maintenance of Adult Myofibers and Their Neuromuscular Junctions

2015 ◽  
Vol 35 (7) ◽  
pp. 1238-1253 ◽  
Author(s):  
Bonnie Seaberg ◽  
Gabrielle Henslee ◽  
Shuo Wang ◽  
Ximena Paez-Colasante ◽  
Gary E. Landreth ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tibialis Anterior ◽  
Neuromuscular Junctions ◽  
Germ Line ◽  
Fiber Type ◽  
Postnatal Growth ◽  
Mammalian Skeletal Muscle ◽  
Neuromuscular Synapses ◽  
Extracellular Signal

The Ras–extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway appears to be important for the development, maintenance, aging, and pathology of mammalian skeletal muscle. Yet no gene targeting ofErk1/2in muscle fibersin vivohas been reported to date. We combined a germ lineErk1mutation with Cre-loxPErk2inactivation in skeletal muscle to produce, for the first time, mice lacking ERK1/2 selectively in skeletal myofibers. Animals lacking muscle ERK1/2 displayed stunted postnatal growth, muscle weakness, and a shorter life span. Their muscles examined in this study, sternomastoid and tibialis anterior, displayed fragmented neuromuscular synapses and a mixture of modest fiber atrophy and loss but failed to show major changes in fiber type composition or absence of cell surface dystrophin. Whereas the lack of only ERK1 had no effects on the phenotypes studied, the lack of myofiber ERK2 explained synaptic fragmentation in the sternomastoid but not the tibialis anterior and a decrease in the expression of the acetylcholine receptor (AChR) epsilon subunit gene mRNA in both muscles. A reduction in AChR protein was documented in line with the above mRNA results. Evidence of partial denervation was found in the sternomastoid but not the tibialis anterior. Thus, myofiber ERK1/2 are differentially required for the maintenance of myofibers and neuromuscular synapses in adult mice.

scholarly journals Microtubules that form the stationary lattice of muscle fibers are dynamic and nucleated at Golgi elements

2013 ◽  
Vol 203 (2) ◽  
pp. 205-213 ◽  
Author(s):  
Sarah Oddoux ◽  
Kristien J. Zaal ◽  
Victoria Tate ◽  
Aster Kenea ◽  
Shuktika A. Nandkeolyar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Muscle ◽  
Muscle Diseases ◽  
Superresolution Microscopy ◽  
Nuclear Membranes ◽  
Organizing Center ◽  
Static Images

Skeletal muscle microtubules (MTs) form a nonclassic grid-like network, which has so far been documented in static images only. We have now observed and analyzed dynamics of GFP constructs of MT and Golgi markers in single live fibers and in the whole mouse muscle in vivo. Using confocal, intravital, and superresolution microscopy, we find that muscle MTs are dynamic, growing at the typical speed of ∼9 µm/min, and forming small bundles that build a durable network. We also show that static Golgi elements, associated with the MT-organizing center proteins γ-tubulin and pericentrin, are major sites of muscle MT nucleation, in addition to the previously identified sites (i.e., nuclear membranes). These data give us a framework for understanding how muscle MTs organize and how they contribute to the pathology of muscle diseases such as Duchenne muscular dystrophy.

scholarly journals In vivo Skeletal Muscle Function and Doxorubicin Treatment in the Rat

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
David Hydock ◽  
Asma Omar ◽  
Eric Bredahl ◽  
Colin Quinn
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Skeletal Muscle Function ◽  
Doxorubicin Treatment

scholarly journals The Influence of Supplemental Dietary Linoleic Acid on Skeletal Muscle Contractile Function in a Rodent Model of Barth Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Mario Elkes ◽  
Martin Andonovski ◽  
Daislyn Vidal ◽  
Madison Farago ◽  
Ryan Modafferi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Linoleic Acid ◽  
Muscle Function ◽  
Barth Syndrome ◽  
Dietary Linoleic Acid ◽  
Skeletal Muscle Function ◽  
Contractile Phenotype ◽  
Muscle Contractile

Barth syndrome is a rare and incurable X-linked (male-specific) genetic disease that affects the protein tafazzin (Taz). Taz is an important enzyme responsible for synthesizing biologically relevant cardiolipin (for heart and skeletal muscle, cardiolipin rich in linoleic acid), a critical phospholipid of mitochondrial form and function. Mutations to Taz cause dysfunctional mitochondria, resulting in exercise intolerance due to skeletal muscle weakness. To date, there has been limited research on improving skeletal muscle function, with interventions focused on endurance and resistance exercise. Previous cell culture research has shown therapeutic potential for the addition of exogenous linoleic acid in improving Taz-deficient mitochondrial function but has not been examined in vivo. The purpose of this study was to examine the influence of supplemental dietary linoleic acid on skeletal muscle function in a rodent model of Barth syndrome, the inducible Taz knockdown (TazKD) mouse. One of the main findings was that TazKD soleus demonstrated an impaired contractile phenotype (slower force development and rates of relaxation) in vitro compared to their WT littermates. Interestingly, this impaired contractile phenotype seen in vitro did not translate to altered muscle function in vivo at the whole-body level. Also, supplemental linoleic acid attenuated, to some degree, in vitro impaired contractile phenotype in TazKD soleus, and these findings appear to be partially mediated by improvements in cardiolipin content and resulting mitochondrial supercomplex formation. Future research will further examine alternative mechanisms of dietary supplemental LA on improving skeletal muscle contractile dysfunction in TazKD mice.

scholarly journals Translocation and clustering of endosomes and lysosomes depends on microtubules.

1987 ◽  
Vol 105 (3) ◽  
pp. 1253-1265 ◽  
Author(s):  
R Matteoni ◽  
T E Kreis
Keyword(s):  
Rat Kidney ◽  
Living Cells ◽  
Cytochalasin D ◽  
Microtubule Organizing Center ◽  
Enhanced Fluorescence ◽  
Organelle Movement ◽  
Organizing Center ◽  
Normal Rat ◽  
Immunofluorescence Labeling

Indirect immunofluorescence labeling of normal rat kidney (NRK) cells with antibodies recognizing a lysosomal glycoprotein (LGP 120; Lewis, V., S.A. Green, M. Marsh, P. Vihko, A. Helenius, and I. Mellman, 1985, J. Cell Biol., 100:1839-1847) reveals that lysosomes accumulate in the region around the microtubule-organizing center (MTOC). This clustering of lysosomes depends on microtubules. When the interphase microtubules are depolymerized by treatment of the cells with nocodazole or during mitosis, the lysosomes disperse throughout the cytoplasm. Lysosomes recluster rapidly (within 30-60 min) in the region of the centrosomes either upon removal of the drug, or, in telophase, when repolymerization of interphase microtubules has occurred. During this translocation process the lysosomes can be found aligned along centrosomal microtubules. Endosomes and lysosomes can be visualized by incubating living cells with acridine orange. We have analyzed the movement of these labeled endocytic organelles in vivo by video-enhanced fluorescence microscopy. Translocation of endosomes and lysosomes occurs along linear tracks (up to 10 microns long) by discontinuous saltations (with velocities of up to 2.5 microns/s). Organelles move bidirectionally with respect to the MTOC. This movement ceases when microtubules are depolymerized by treatment of the cells with nocodazole. After nocodazole washout and microtubule repolymerization, the translocation and reclustering of fluorescent organelles predominantly occurs in a unidirectional manner towards the area of the MTOC. Organelle movement remains unaffected when cells are treated with cytochalasin D, or when the collapse of intermediate filaments is induced by microinjected monoclonal antivimentin antibodies. It can be concluded that translocation of endosomes and lysosomes occurs along microtubules and is independent of the intermediate filament and microfilament networks.

scholarly journals The effect of obesity on the contractile performance of isolated mouse soleus, EDL, and diaphragm muscles

2017 ◽  
Vol 122 (1) ◽  
pp. 170-181 ◽  
Author(s):  
Jason Tallis ◽  
Cameron Hill ◽  
Rob S. James ◽  
Val M. Cox ◽  
Frank Seebacher
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Isometric Force ◽  
Muscle Performance ◽  
Muscle Quality ◽  
Control Group ◽  
Protein Kinase Activity ◽  
Negative Cycle ◽  
Contractile Performance

Obesity affects the major metabolic and cellular processes involved in skeletal muscle contractility. Surprisingly, the effect of obesity on isolated skeletal muscle performance remains unresolved. The present study is the first to examine the muscle-specific changes in contractility following dietary-induced obesity using an isolated muscle work-loop (WL) model that more closely represents in vivo muscle performance. Following 16-wk high-calorific feeding, soleus (SOL), extensor digitorum longus (EDL), and diaphragm (DIA) were isolated from female (CD-1) mice, and contractile performance was compared against a lean control group. Obese SOL produced greater isometric force; however, isometric stress (force per unit muscle area), absolute WL power, and normalized WL power (watts per kilogram muscle mass) were unaffected. Maximal isometric force and absolute WL power of the EDL were similar between groups. For both EDL and DIA, isometric stress and normalized WL power were reduced in the obese groups. Obesity caused a significant reduction in fatigue resistance in all cases. Our findings demonstrate a muscle-specific reduction in contractile performance and muscle quality that is likely related to in vivo mechanical role, fiber type, and metabolic profile, which may in part be related to changes in myosin heavy chain expression and AMP-activated protein kinase activity. These results infer that, beyond the additional requirement of moving a larger body mass, functional performance and quality of life may be further limited by poor muscle function in obese individuals. As such, a reduction in muscle performance may be a substantial contributor to the negative cycle of obesity. NEW & NOTEWORTHY The effect of obesity on isolated muscle function is surprisingly underresearched. The present study is the first to examine the effects of obesity on isolated muscle performance using a method that more closely represents real-world muscle function. This work uniquely establishes a muscle-specific profile of mechanical changes in relation to underpinning mechanisms. These findings may be important to understanding the negative cycle of obesity and in designing interventions for improving weight status.

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