Muscle intermediate filaments and their links to membranes and membranous organelles. Exp Cell Res

Cell Biology Division, Center of Basic Research, Biomedical Research Foundation Academy of Athens, Soranou Efessiou 4, 12965 Athens, Greece.
Experimental Cell Research (Impact Factor: 3.25). 07/2007; 313(10):2063-76. DOI: 10.1016/j.yexcr.2007.03.033
Source: PubMed


Intermediate filaments (IFs) play a key role in the integration of structure and function of striated muscle, primarily by mediating mechanochemical links between the contractile apparatus and mitochondria, myonuclei, the sarcolemma and potentially the vesicle trafficking apparatus. Linkage of all these membranous structures to the contractile apparatus, mainly through the Z-disks, supports the integration and coordination of growth and energy demands of the working myocyte, not only with force transmission, but also with de novo gene expression, energy production and efficient protein and lipid trafficking and targeting. Desmin, the most abundant and intensively studied muscle intermediate filament protein, is linked to proper costamere organization, myoblast and stem cell fusion and differentiation, nuclear shape and positioning, as well as mitochondrial shape, structure, positioning and function. Similar links have been established for lysosomes and lysosome-related organelles, consistent with the presence of widespread links between IFs and membranous structures and the regulation of their fusion, morphology and stabilization necessary for cell survival.

Download full-text


Available from: Robert J Bloch, Feb 26, 2015
    • "These proteins play an important role in sarcomeric movements by linking the contractile apparatus to the sarcolemma and extracellular matrix (ECM). The cytoskeleton also has important roles in cell shape, signal transduction, growth, division and differentiation , as well as in the movement of organelles within the cell (Capetanaki et al. 2007). In skeletal muscles the major elements of the cytoskeleton are the intermediate filaments (IFs; Paulin & Li, 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The human oropharyngeal muscles have a unique anatomy with diverse and intricate functions. To investigate if this specialization is also reflected in the cytoarchitecture of muscle fibers, intermediate filament proteins and the dystrophin-associated protein complex have been analyzed in two human palate muscles, musculus uvula (UV) and musculus palatopharyngeus (PP), with immunohistochenmical and morphological techniques. Human limb muscles were used as reference. The findings show that the soft palate muscle fibers have a cytoskeletal architecture that differs from the limb muscles. While all limb muscles showed immunoreaction for a panel of antibodies directed against different domains of cytoskeletal proteins desmin and dystrophin, a subpopulation of palate muscle fibers lacked or had a faint immunoreaction for desmin (UV 11.7% and PP 9.8%) and the C-terminal of the dystrophin molecule (UV 4.2% and PP 6.4%). The vast majority of these fibers expressed slow contractile protein myosin heavy chain I. Furthermore, an unusual staining pattern was also observed in these fibers for β-dystroglycan, caveolin-3 and neuronal nitric oxide synthase nNOS, which are all membrane-linking proteins associated with the dystrophin C-terminus. While the immunoreaction for nNOS was generally weak or absent, β-dystroglycan and caveolin-3 showed a stronger immunostaining. The absence or a low expression of cytoskeletal proteins otherwise considered ubiquitous and important for integration and contraction of muscle cells indicate a unique cytoarchitecture designed to meet the intricate demands of the upper airway muscles. It can be concluded that a subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties, and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles.
    No preview · Article · Dec 2015
  • Source
    • "AGEs and lipid peroxidation end-products accumulate in PAD muscle and, particularly, in PAD myofibers (Norgren et al. 2007; Pipinos et al. 2008, 2007). Desmin links neighboring myofibrils into bundles through their Z-discs (Capetanaki et al. 2007; Dalakas et al. 2000), aligns the Z-discs of neighboring myofibers (Capetanaki et al. 1997; Carlsson and Thornell 2001; Lazarides 1980), organizes the mitochondria into a welldefined functional network around the myofibrils (Capetanaki et al. 1997; Milner et al. 2000) and facilitates transmission of the force of sarcomere contraction to the ECM (Bloch and Gonzalez-Serratos 2003; Capetanaki et al. 2007; Carlsson and Thornell 2001; Goldfarb et al. 2004; Paulin et al. 2004). Mitochondrial dysfunction in PAD skeletal muscle is well documented (Makris et al. 2007; Pipinos et al. 2006; Pipinos et al. 2003; Pipinos et al. 2000). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with peripheral artery disease (PAD) develop a myopathy in their ischemic lower extremities, which is characterized by myofiber degeneration, mitochondrial dysfunction and impaired limb function. Desmin, a protein of the cytoskeleton, is central to maintenance of the structure, shape and function of the myofiber and its organelles, especially the mitochondria, and to translation of sarcomere contraction into muscle contraction. In this study, we investigated the hypothesis that disruption of the desmin network occurs in gastrocnemius myofibers of PAD patients and correlates with altered myofiber morphology, mitochondrial dysfunction, and impaired limb function. Using fluorescence microscopy, we evaluated desmin organization and quantified myofiber content in the gastrocnemius of PAD and control patients. Desmin was highly disorganized in PAD but not control muscles and myofiber content was increased significantly in PAD compared to control muscles. By qPCR, we found that desmin gene transcripts were increased in the gastrocnemius of PAD patients as compared with control patients. Increased desmin and desmin gene transcripts in PAD muscles correlated with altered myofiber morphology, decreased mitochondrial respiration, reduced calf muscle strength and decreased walking performance. In conclusion, our studies identified disruption of the desmin system in gastrocnemius myofibers as an index of the myopathy and limitation of muscle function in patients with PAD.
    Full-text · Article · Jan 2015 · Journal of Histochemistry and Cytochemistry
  • Source
    • "Based on reported physical interactions in the literature and protein-protein interaction databases (BioGRID, MINT, GeneMANIA; Mostafavi et al. 2008; Stark et al. 2006), we established an interaction network for desmin (Fig. 2b). Desmin interactors include other members of the IF family, cytolinkers bridging organelles and cytoskeleton, chaperones and adaptor proteins and proteins that have been implicated in proteolysis, posttranslational modifications and signaling important for proper skeletal or cardiac muscle functions (Capetanaki et al. 2007; Costa et al. 2004). The architectural role of desmin filaments has been enriched by these new findings suggesting that desmin serves as a platform for signaling events perturbed upon desmin misfolding/ aggregation under pathological conditions. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Desmin is a muscle-specific type III intermediate filament essential for proper muscular structure and function. In human, mutations affecting desmin expression or promoting its aggregation lead to skeletal (desmin-related myopathies), or cardiac (desmin-related cardiomyopathy) phenotypes, or both. Patient muscles display intracellular accumulations of misfolded proteins and desmin-positive insoluble granulofilamentous aggregates, leading to a large spectrum of molecular alterations. Increasing evidence shows that desmin function is not limited to the structural and mechanical integrity of cells. This novel perception is strongly supported by the finding that diseases featuring desmin aggregates cannot be easily associated with mechanical defects, but rather involve desmin filaments in a broader spectrum of functions, such as in organelle positioning and integrity and in signaling. Here, we review desmin functions and related diseases affecting striated muscles. We detail emergent cellular functions of desmin based on reported phenotypes in patients and animal models. We discuss known desmin protein partners and propose an overview of the way that this molecular network could serve as a signal transduction platform necessary for proper muscle function.
    Full-text · Article · Oct 2014 · Cell and Tissue Research
Show more