Cytoskeleton and Adhesion in Myogenesis

The function of muscle is to contract, which means to exert force on a substrate. The adaptations required for skeletal muscle differentiation, from a prototypic cell, involve specialization of housekeeping cytoskeletal contracting and supporting systems into crystalline arrays of proteins. Here I discuss the changes that all three cytoskeletal systems (microfilaments, intermediate filaments, and microtubules) undergo through myogenesis. I also discuss their interaction, through the membrane, to extracellular matrix and to other cells, where force will be exerted during contraction. The three cytoskeletal systems are necessary for the muscle cell and must exert complementary roles in the cell. Muscle is a responsive system, where structure and function are integrated: the structural adaptations it undergoes depend on force production. In this way, the muscle cytoskeleton is a portrait of its physiology. I review the cytoskeletal proteins and structures involved in muscle function and focus particularly on their role in myogenesis, the process by which this incredible muscle machine is made. Although the focus is on skeletal muscle, some of the discussion is applicable to cardiac and smooth muscle.

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Mitochondrial dysfunction and insulin resistance from the outside in: extracellular matrix, the cytoskeleton, and mitochondria

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00363.2011 ◽

2011 ◽

Vol 301 (5) ◽

pp. E749-E755 ◽

Cited By ~ 55

Author(s):

Dawn K. Coletta ◽

Lawrence J. Mandarino

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Extracellular Matrix ◽

Contractile Activity ◽

Cytoskeletal Proteins ◽

Altered Expression ◽

Insulin Resistant ◽

And Function

Insulin resistance in skeletal muscle is a prominent feature of obesity and type 2 diabetes. The association between mitochondrial changes and insulin resistance is well known. More recently, there is growing evidence of a relationship between inflammation, extracellular remodeling, and insulin resistance. The intent of this review is to propose a potentially novel mechanism for the development of insulin resistance, focusing on the underappreciated connections among inflammation, extracellular remodeling, cytoskeletal interactions, mitochondrial function, and insulin resistance in human skeletal muscle. Several sources of inflammation, including expansion of adipose tissue resulting in increased lipolysis and alterations in pro- and anti-inflammatory cytokines, contribute to the insulin resistance observed in obesity and type 2 diabetes. In the experimental model of lipid oversupply, an inflammatory response in skeletal muscle leads to altered expression extracellular matrix-related genes as well as nuclear encoded mitochondrial genes. A similar pattern also is observed in “naturally” occurring insulin resistance in muscle of obese nondiabetic individuals and patients with type 2 diabetes mellitus. More recently, alterations in proteins (including α-actinin-2, desmin, proteasomes, and chaperones) involved in muscle structure and function have been observed in insulin-resistant muscle. Some of these cytoskeletal proteins are mechanosignal transducers that allow muscle fibers to sense contractile activity and respond appropriately. The ensuing alterations in expression of genes coding for mitochondrial proteins and cytoskeletal proteins may contribute to the mitochondrial changes observed in insulin-resistant muscle. These changes in turn may lead to a reduction in fat oxidation and an increase in intramyocellular lipid, which contributes to the defects in insulin signaling in insulin resistance.

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Structure and function of the skeletal muscle extracellular matrix

Muscle & Nerve ◽

10.1002/mus.22094 ◽

2011 ◽

Vol 44 (3) ◽

pp. 318-331 ◽

Cited By ~ 355

Author(s):

Allison R. Gillies ◽

Richard L. Lieber

Keyword(s):

Skeletal Muscle ◽

Extracellular Matrix ◽

Structure And Function ◽

And Function

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CURRENT TOPICS FOR TEACHING SKELETAL MUSCLE PHYSIOLOGY

AJP Advances in Physiology Education ◽

10.1152/advan.2003.27.4.171 ◽

2003 ◽

Vol 27 (4) ◽

pp. 171-182

Author(s):

Susan V. Brooks

Keyword(s):

Skeletal Muscle ◽

Muscle Function ◽

Structure And Function ◽

Muscle Physiology ◽

American Physiological Society ◽

Skeletal Muscle Function ◽

Teaching Resources ◽

Muscle Structure ◽

The Stability ◽

And Function

Contractions of skeletal muscles provide the stability and power for all body movements. Consequently, any impairment in skeletal muscle function results in some degree of instability or immobility. Factors that influence skeletal muscle structure and function are therefore of great interest both scientifically and clinically. Injury, disease, and old age are among the factors that commonly contribute to impairment in skeletal muscle function. The goal of this article is to update current concepts of skeletal muscle physiology. Particular emphasis is placed on mechanisms of injury, repair, and adaptation in skeletal muscle as well as mechanisms underlying the declining skeletal muscle structure and function associated with aging. For additional materials please refer to the “Skeletal Muscle Physiology” presentation located on the American Physiological Society Archive of Teaching Resources Web site ( https://www.lifescitrc.org ).

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Extracellular Matrix Components and Integrins in the Control of Arterial Smooth Muscle Cell Structure and Function

Journal of Atherosclerosis and Thrombosis ◽

10.5551/jat1994.1.supplemment1_s39 ◽

1994 ◽

Vol 1 (Supplemment1) ◽

pp. S39-S46 ◽

Cited By ~ 1

Author(s):

Ulf Hedin

Keyword(s):

Extracellular Matrix ◽

Smooth Muscle ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Cell Structure ◽

Structure And Function ◽

Arterial Smooth Muscle Cell ◽

Extracellular Matrix Components ◽

Matrix Components ◽

And Function

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The role of extracellular matrix composition in structure and function of bioengineered skeletal muscle

Biomaterials ◽

10.1016/j.biomaterials.2011.01.062 ◽

2011 ◽

Vol 32 (14) ◽

pp. 3575-3583 ◽

Cited By ~ 149

Author(s):

Sara Hinds ◽

Weining Bian ◽

Robert G. Dennis ◽

Nenad Bursac

Keyword(s):

Skeletal Muscle ◽

Extracellular Matrix ◽

Structure And Function ◽

Matrix Composition ◽

And Function

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New Insights into the Structural Roles of Nebulin in Skeletal Muscle

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/968139 ◽

2010 ◽

Vol 2010 ◽

pp. 1-6 ◽

Cited By ~ 15

Author(s):

Coen A. C. Ottenheijm ◽

Henk Granzier

Keyword(s):

Skeletal Muscle ◽

Thin Filament ◽

Force Production ◽

Nemaline Myopathy ◽

Structure And Function ◽

Filament Length ◽

Thin Filaments ◽

Muscle Structure ◽

And Function

One important feature of muscle structure and function that has remained relatively obscure is the mechanism that regulates thin filament length. Filament length is an important aspect of muscle function as force production is proportional to the amount of overlap between thick and thin filaments. Recent advances, due in part to the generation of nebulin KO models, reveal that nebulin plays an important role in the regulation of thin filament length. Another structural feature of skeletal muscle that is not well understood is the mechanism involved in maintaining the regular lateral alignment of adjacent sarcomeres, that is, myofibrillar connectivity. Recent studies indicate that nebulin is part of a protein complex that mechanically links adjacent myofibrils. Thus, novel structural roles of nebulin in skeletal muscle involve the regulation of thin filament length and maintaining myofibrillar connectivity. When these functions of nebulin are absent, muscle weakness ensues, as is the case in patients with nemaline myopathy with mutations in nebulin. Here we review these new insights in the role of nebulin in skeletal muscle structure.

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Effects of Dexamethasone Dose and Timing on Tissue-Engineered Skeletal Muscle Units

Cells Tissues Organs ◽

10.1159/000490884 ◽

2018 ◽

Vol 205 (4) ◽

pp. 197-207 ◽

Cited By ~ 4

Author(s):

Alexie A. Larson ◽

Brian C. Syverud ◽

Shelby E. Florida ◽

Brittany L. Rodriguez ◽

Molly N. Pantelic ◽

...

Keyword(s):

Skeletal Muscle ◽

Cell Proliferation ◽

Force Production ◽

Structure And Function ◽

Tetanic Force ◽

Time Points ◽

Early Differentiation ◽

Brdu Assay ◽

And Function ◽

Precise Time

Our lab showed that administration of dexamethasone (DEX) stimulated myogenesis and resulted in advanced structure in our engineered skeletal muscle units (SMU). While administration of 25 nM DEX resulted in the most advanced structure, 10 nM dosing resulted in the greatest force production. We hypothesized that administration of 25 nM DEX during the entire fabrication process was toxic to the cells and that administration of DEX at precise time points during myogenesis would result in SMU with a more advanced structure and function. Thus, we fabricated SMU with 25 nM DEX administered at early proliferation (days 0–4), late proliferation (days 3–5), and early differentiation (days 5–7) stages of myogenesis and compared them to SMU treated with 10 nM DEX (days 0–16). Cell proliferation was measured with a BrdU assay (day 4) and myogenesis was examined by immunostaining for MyoD (day 4), myogenin (day 7), and α-actinin (day 11). Following SMU formation, isometric tetanic force production was measured. An analysis of cell proliferation indicated that 25 nM DEX administered at early proliferation (days 0–4) provided 21.5% greater myogenic proliferation than 10 nM DEX (days 0–4). In addition, 25 nM DEX administered at early differentiation (days 5–7) showed the highest density of myogenin-positive cells, demonstrating the greatest improvement in differentiation of myoblasts. However, the most advanced sarcomeric structure and the highest force production were exhibited with sustained administration of 10 nM DEX (days 0–16). In conclusion, alteration of the timing of 25 nM DEX administration did not enhance the structure or function of our SMU. SMU were optimally fabricated with sustained administration of 10 nM DEX.

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