Plectin 1f scaffolding at the sarcolemma of dystrophic (<i>mdx</i>) muscle fibers through multiple interactions with β-dystroglycan

Rezniczek, Günther A.; Konieczny, Patryk; Nikolic, Branislav; Reipert, Siegfried; Schneller, Doris; Abrahamsberg, Christina; Davies, Kay E.; Winder, Steve J.; Wiche, Gerhard

doi:10.1083/jcb.200604179

Cited by 142 publications

(204 citation statements)

References 49 publications

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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).…”

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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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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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“…This partial visibility is likely due to interactions with other partners apart from dystrophin, such as utrophin or plectin. Utrophin is over-expressed in DMD and mdx mouse muscle, and is able to bind to β-dystroglycan [25,36], while plectin is a newly revealed partner of β-dystroglycan [51]. We propose that the direct interaction between these two proteins and β-dystroglycan could explain the remaining partial visibility of the β-dystroglycan in mdx mouse muscle.…”

Section: Discussionmentioning

confidence: 98%

Several dystrophin-glycoprotein complex members are present in crude surface membranes but they are sodium dodecyl sulphate invisible in KCl-washed microsomes from mdx mouse muscle

Daval

Rocher²,

Chérel

et al. 2010

Cellular and Molecular Biology Letters

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The dystrophin-glycoprotein complex (DGC) is a large transsarcolemmal complex that provides a linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. In skeletal muscle, it consists of the dystroglycan, sarcoglycan and cytoplasmic complexes, with dystrophin forming the core protein. The DGC has been described as being absent or greatly reduced in dystrophin-deficient muscles, and this lack is considered to be involved in the dystrophic phenotype. Such a decrease in the DGC content was observed in dystrophin-deficient muscle from humans with muscular dystrophy and in mice with X-linked muscular dystrophy (mdx mice). These deficits were observed in total muscle homogenates and in partially membrane-purified muscle fractions, the so-called KCl-washed microsomes. Here, we report that most of the proteins of the DGC are actually present at normal levels in the mdx mouse muscle plasma membrane. The proteins are detected in dystrophic animal muscles when the immunoblot assay is performed with crude surface membrane fractions instead of the usually employed KCl-washed microsomes. We propose that these proteins form SDS-insoluble membrane complexes when dystrophin is absent.

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“…It is unlikely that there is a direct interaction between the AMPK and dystroglycan. Although AMPK and its upstream kinase LKB1 are located throughout the cytosol and in the nucleus, two recent reports have identified plectin as an AMPK and a dystroglycan binding partner (29,30). Plectin is a highmolecular-weight, cytoskeleton-associated protein with a broad tissue and cell expression pattern (31).…”

Section: Discussionmentioning

confidence: 99%

Stretch-Induced Activation of AMP Kinase in the Lung Requires Dystroglycan

Budinger¹,

Urich²,

DeBiase³

et al. 2008

Am J Respir Cell Mol Biol

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Lung cells are exposed to cyclic stretch during normal respiration and during positive pressure mechanical ventilation administered to support gas exchange. Dystroglycan is a ubiquitously expressed matrix receptor that is required for normal basement membrane formation during embryogenesis and for maintaining the function of skeletal muscle myocytes and neurons where it links cells to matrix. We previously reported that equibiaxial stretch of primary alveolar epithelial cells activated the MAP kinase pathway ERK1/2 through a mechanism that required an interaction between dystroglycan and matrix. We determined whether this mechanism of mechanotransduction activates other signaling cascades in lung epithelium. Exposure of rat epithelial alveolar type II cells (AEC) to cyclic mechanical stretch resulted in activation of 59 AMP-activated protein kinase (AMPK). This response was not affected by pretreatment of AEC with the ERK inhibitor PD98059 but was inhibited by knockdown in dystroglycan expression. Moreover, production of reactive oxygen species was enhanced in mechanically stimulated AEC in which dystroglycan was knocked down. This enhancement was reversed by treatment of AEC with an AMPK activator. Activation of AMPK was also observed in lung homogenates from mice after 15 minutes of noninjurious mechanical ventilation. Furthermore, knockdown of dystroglycan in the lungs of mice using an adenovirus encoding a dystroglycan shRNA prevented the stretch-induced activation of AMPK. These results suggest that exposure to cyclic stretch activates the metabolic sensing pathway AMPK in the lung epithelium and supports a novel role for dystroglycan in this mechanotransduction.

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Plectin 1f scaffolding at the sarcolemma of dystrophic (mdx) muscle fibers through multiple interactions with β-dystroglycan

Cited by 142 publications

References 49 publications

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

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

Several dystrophin-glycoprotein complex members are present in crude surface membranes but they are sodium dodecyl sulphate invisible in KCl-washed microsomes from mdx mouse muscle

Stretch-Induced Activation of AMP Kinase in the Lung Requires Dystroglycan

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