Plectin 1 links intermediate filaments to costameric sarcolemma through β-synemin, α-dystrobrevin and actin

Hijikata, Takao; Nakamura, Akio; Isokawa, Keitaro; Imamura, Michihiro; Yuasa, Katsutoshi; Ishikawa, Ryoki; Kohama, Kazuhiro; Takeda, Shin‐ichi; Yorifuji, Hiroshi

doi:10.1242/jcs.021634

Cited by 56 publications

(63 citation statements)

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“…8B. At lower stimulation frequencies (30,40, and 60 Hz), there was no significant difference between control and synm-null mice. This result suggests that force production in fast-twitch muscle decreased a small but significant extent in synm-null mice.…”

Section: Resultsmentioning

confidence: 82%

“…These were elicited to establish contractile responses before any additional experimental procedures were performed. With muscles set at L o, we gradually increased the stimulation frequency to establish a forcefrequency relationship (10,30,40,60,80, and 100 Hz). We used the value that gave 100% maximal stimulation intensity to induce maximal force (P o).…”

Section: Methodsmentioning

confidence: 99%

“…Unlike desmin and keratins, which are small IF proteins (40 -70 kDa), synemin is large, due to its long COOH-terminal domain, and it can be expressed in either ␣ (ϳ210 kDa)-or ␤ (ϳ180 kDa)-isoforms (3,7,8), generated by alternative splicing. In addition to desmin, synemin can associate with keratin IFs and with the costameric proteins ␣-dystrobrevin, dystrophin, utrophin, vinculin, and talin, as well as with ␣-actinin at Z disks (4,17,35,40,59,90,91). Synemin therefore has the potential to link costameres to the contractile apparatus at Z disks.…”

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confidence: 99%

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Myopathic changes in murine skeletal muscle lacking synemin

García‐Pelagio

Muriel

O’Neill

et al. 2015

American Journal of Physiology-Cell Physiology

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(IF) proteins are associated with defects in the organization of the contractile apparatus and its links to costameres, which connect the sarcomeres to the cell membrane. Here we study the role in skeletal muscle of synemin, a type IV IF protein, by examining mice null for synemin (synm-null). Synm-null mice have a mild skeletal muscle phenotype. Tibialis anterior (TA) muscles show a significant decrease in mean fiber diameter, a decrease in twitch and tetanic force, and an increase in susceptibility to injury caused by lengthening contractions. Organization of proteins associated with the contractile apparatus and costameres is not significantly altered in the synm-null. Elastimetry of the sarcolemma and associated contractile apparatus in extensor digitorum longus myofibers reveals a reduction in tension consistent with an increase in sarcolemmal deformability. Although fatigue after repeated isometric contractions is more marked in TA muscles of synm-null mice, the ability of the mice to run uphill on a treadmill is similar to controls. Our results suggest that synemin contributes to linkage between costameres and the contractile apparatus and that the absence of synemin results in decreased fiber size and increased sarcolemmal deformability and susceptibility to injury. Thus synemin plays a moderate but distinct role in fast twitch skeletal muscle. cytoskeleton; costameres; elastimetry; biomechanical properties; desmin A LARGE NUMBER OF HUMAN DISEASES, ranging from skin disorders (51), to premature aging (34, 64), to skeletal and cardiac myopathies (19,37), are linked to mutations in genes encoding intermediate filament (IF) proteins (25). Since the discovery of desmin, the major IF protein of striated muscle (49), its role and that of other IF proteins in muscle have been of keen interest to many laboratories (reviewed in 16). Our research on muscle IF proteins has addressed their role in force transmission and in organizing the sarcoplasm and stabilizing it against injury during force generation.Force generated in muscle can be transmitted radially, from the myofibrils, across the sarcolemma to the extracellular matrix and neighboring cells (11, 67). As a result, a significant amount of force is exerted on the sarcolemma and the structures that link it to the underlying contractile apparatus and the extracellular matrix. The ability of the sarcolemma with the underlying contractile apparatus to withstand the distortions caused during isotonic contractions (2, 11, 12) depends on specialized structures, termed "costameres" (66), that mediate the radial transmission of force across the sarcolemma (11). Costameres are structures at the sarcolemma of striated muscle fibers that align circumferentially around the Z disks and the M bands of the nearest myofibrils, and longitudinally, to form a rectilinear sarcolemmal network comprised of integral membrane proteins (such as dystroglycan, the sarcoglycans, and Na-K-ATPase), proteins of the extracellular matrix (such as laminin and collagen IV), and proteins of t...

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Section: Resultsmentioning

confidence: 82%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Myopathic changes in murine skeletal muscle lacking synemin

García‐Pelagio

Muriel

O’Neill

et al. 2015

American Journal of Physiology-Cell Physiology

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“…Plectin is also localized at the desmosomes (9), which mediate cell-cell contacts, and connects the nuclear envelope to the intermediate filaments by binding to the outer nuclear membrane protein nesprin-3␣ (10 -11). In striated muscle, plectin is localized at the Z-line and the costameres, where it associates with the intermediate filament protein desmin and with components of the dystrophin glycoprotein complex (12)(13)(14)(15). The contribution of plectin to preserve the integrity of tissues that are exposed to mechanical stress is illustrated by the effect of mutations in the PLEC gene, which lead to a severe skin blistering disease called epidermolysis bullosa simplex that is characterized by defects at the level of the hemidesmosomal cell-basal membrane junction and is frequently associated with late-onset muscular dystrophy (16 -17).…”

mentioning

confidence: 99%

“…The plakin domain of plectin and other plakins contain protein-protein interaction sites and they are important for the localization of plakins at junctional complexes. In plectin this region harbors binding sites for the integrin ␤4 subunit (24), the cytoplasmic domain of BPAG2 (25), ␤-dystroglycan (13), ␤-synemin (15), and the tyrosine kinase Fer (26). The central region consists of a coiled-coil rod domain that acts as a structural spacer of the protein-protein binding sites located in the N-and C-terminal regions and mediates homodimerization of plectin.…”

mentioning

confidence: 99%

The Structure of the Plakin Domain of Plectin Reveals a Non-canonical SH3 Domain Interacting with Its Fourth Spectrin Repeat

Ortega

Buey

Sonnenberg

et al. 2011

Journal of Biological Chemistry

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Plectin belongs to the plakin family of cytoskeletal crosslinkers, which is part of the spectrin superfamily. Plakins contain an N-terminal conserved region, the plakin domain, which is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. We have combined x-ray crystallography and small angle x-ray scattering (SAXS) to elucidate the structure of the central region of the plakin domain of plectin, which corresponds to the SR3, SR4, SR5, and SH3 domains. The crystal structures of the SR3-SR4 and SR4-SR5-SH3 fragments were determined to 2.2 and 2.95 Å resolution, respectively. The SH3 of plectin presents major alterations as compared with canonical Pro-rich binding SH3 domains, suggesting that plectin does not recognize Pro-rich motifs. In addition, the SH3 binding site is partially occluded by an intramolecular contact with the SR4. Residues of this pseudobinding site and the SR4/SH3 interface are conserved within the plakin family, suggesting that the structure of this part of the plectin molecule is similar to that of other plakins. We have created a model for the SR3-SR4-SR5-SH3 region, which agrees well with SAXS data in solution. The three SRs form a semi-flexible rod that is not altered by the presence of the SH3 domain, and it is similar to those found in spectrins. The flexibility of the plakin domain, in analogy with spectrins, might contribute to the role of plakins in maintaining the stability of tissues subject to mechanical stress.Plakins are a family of high molecular weight proteins that interconnect elements of the cytoskeleton and tether them to membrane-associated structures; hence, they are also known as cytolinkers (1-2). Mammalian plakins include desmoplakin, plectin, the bullous pemphigoid antigen 1 (BPAG1), 4 the microtubule actin crosslinking factor 1 (MACF1, also known as ACF7, trabeculin, or macrophin), envoplakin, periplakin, and epiplakin. Plakins are also present in invertebrates; Drosophila melanogaster has a single plakin gene named shortstop (also know as kakapo) that encodes at least two protein forms, Shot I and Shot II. Similarly, the only plakin gene in Caenorhabditis elegans, vab-10, encodes two variants VAB-10A and VAB-10B.Plectin is a highly versatile plakin that associates with intermediate filaments (3), microtubules (4), and actin fibers (5), and crosslinks these cytoskeletal networks (5-6). Plectin also connects intermediate filaments to membrane-associated complexes. In stratified epithelia such as the skin, plectin is localized at the hemidesmosomes, which are junctional complexes that link the intermediate filaments to the basement membrane, and links the integrin ␣6␤4 and the bullous pemphigoid antigen 2 (BPAG2, also known as type XVII collagen or BP180) to the cytokeratins (7-8). Plectin is also localized at the desmosomes (9), which mediate cell-cell contacts, and connects the nuclear envelope to the intermediate filaments by binding to the outer nuclear membrane protein nesprin-3␣ (10 -11). In st...

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Muscle Structure and Cytoskeletal Proteins

Kerth

2013

The Science of Meat Quality

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Plectin 1 links intermediate filaments to costameric sarcolemma through β-synemin, α-dystrobrevin and actin

Abstract: SummaryPlectin 1 links intermediate filaments to costameric sarcolemma through β-synemin, α-dystrobrevin and actin

Cited by 56 publications

References 75 publications

Myopathic changes in murine skeletal muscle lacking synemin

Myopathic changes in murine skeletal muscle lacking synemin

The Structure of the Plakin Domain of Plectin Reveals a Non-canonical SH3 Domain Interacting with Its Fourth Spectrin Repeat

Muscle Structure and Cytoskeletal Proteins

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