Skeletal muscle intermediate filaments form a stress-transmitting and stress-signaling network. 2015

Michelle G Palmisano, and Shannon N Bremner, and Troy A Hornberger, and Gretchen A Meyer, and Andrea A Domenighetti, and Sameer B Shah, and Balázs Kiss, and Miklos Kellermayer, and Allen F Ryan, and Richard L Lieber
Departments of Orthopaedics, Bioengineering, Medicine and the Biomedical Sciences Graduate Group, University of California and Veterans Administration Medical Centers, San Diego, CA 92093, USA.

A fundamental requirement of cells is their ability to transduce and interpret their mechanical environment. This ability contributes to regulation of growth, differentiation and adaptation in many cell types. The intermediate filament (IF) system not only provides passive structural support to the cell, but recent evidence points to IF involvement in active biological processes such as signaling, mechanotransduction and gene regulation. However, the mechanisms that underlie these processes are not well known. Skeletal muscle cells provide a convenient system to understand IF function because the major muscle-specific IF, desmin, is expressed in high abundance and is highly organized. Here, we show that desmin plays both structural and regulatory roles in muscle cells by demonstrating that desmin is required for the maintenance of myofibrillar alignment, nuclear deformation, stress production and JNK-mediated stress sensing. Finite element modeling of the muscle IF system suggests that desmin immediately below the sarcolemma is the most functionally significant. This demonstration of biomechanical integration by the desmin IF system suggests that it plays an active biological role in muscle in addition to its accepted structural role.

UI MeSH Term Description Entries
D007382 Intermediate Filaments Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. Tonofilaments,Neurofilaments,Filament, Intermediate,Filaments, Intermediate,Intermediate Filament,Neurofilament,Tonofilament
D009210 Myofibrils The long cylindrical contractile organelles of STRIATED MUSCLE cells composed of ACTIN FILAMENTS; MYOSIN filaments; and other proteins organized in arrays of repeating units called SARCOMERES . Myofilaments,Myofibril,Myofilament
D003893 Desmin An intermediate filament protein found predominantly in smooth, skeletal, and cardiac muscle cells. Localized at the Z line. MW 50,000 to 55,000 is species dependent. Skeletin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012508 Sarcolemma The excitable plasma membrane of a muscle cell. (Glick, Glossary of Biochemistry and Molecular Biology, 1990) Sarcolemmas
D013314 Stress, Mechanical A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area. Mechanical Stress,Mechanical Stresses,Stresses, Mechanical
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out
D018482 Muscle, Skeletal A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles. Anterior Tibial Muscle,Gastrocnemius Muscle,Muscle, Voluntary,Plantaris Muscle,Skeletal Muscle,Soleus Muscle,Muscle, Anterior Tibial,Muscle, Gastrocnemius,Muscle, Plantaris,Muscle, Soleus,Muscles, Skeletal,Muscles, Voluntary,Skeletal Muscles,Tibial Muscle, Anterior,Voluntary Muscle,Voluntary Muscles
D040542 Mechanotransduction, Cellular The process by which cells convert mechanical stimuli into a chemical response. It can occur in both cells specialized for sensing mechanical cues such as MECHANORECEPTORS, and in parenchymal cells whose primary function is not mechanosensory. Cellular Mechanotransduction,Mechanosensory Transduction,Signal Transduction, Mechanical,Mechanical Signal Transduction,Transduction, Mechanosensory

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