Browsing by Author "Roman, William"
Now showing 1 - 5 of 5
Results Per Page
Sort Options
- Local arrangement of Fibronectin by myofibroblasts governs peripheral nuclear positioning in muscle cellsPublication . Roman, William; Martins, João P.; Gomes, EdgarSkeletal muscle cells (myofibers) are rod-shaped multinucleated cells surrounded by an extracellular matrix (ECM) basal lamina. In contrast to other cell types, nuclei in myofibers are positioned just below the plasma membrane at the cell periphery. Peripheral nuclear positioning occurs during myogenesis and is driven by myofibril crosslinking and contraction. Here we show that peripheral nuclear positioning is triggered by local accumulation of fibronectin secreted by myofibroblasts. We demonstrate that fibronectin via α5-integrin mediates peripheral nuclear positioning dependent on FAK and Src activation. Finally, we show that Cdc42, downstream of restricted fibronectin activation, is required for myofibril crosslinking but not myofibril contraction. Thus we identify that local activation of integrin by fibronectin secreted by myofibroblasts activates peripheral nuclear positioning in skeletal myofibers.
- Muscle is a stage, and cells and factors are merely playersPublication . Roman, William; Muñoz-Cánoves, PuraThe incredible ability of satellite cells to regenerate muscle has captivated much of the research field's attention over the past decades. Versatile, enigmatic, vigorous, and skillful, the satellite cell is the optimal actor to cast in a regenerative epic, grabbing contracts and making headlines. However, the scenarios that play out during normal muscle usage, such as during exercise and aging, diverge from the experimental setup staged to spotlight satellite cells. Recent studies examining myofibers have highlighted novel attributes, including a capacity for self-repair. We discuss here the distinctions between myofiber self-repair and satellite-cell-dependent regeneration and how they may cooperate to repair damage after exercise, in myopathies, and in aging.
- Myofibril contraction and crosslinking drive nuclear movement to the periphery of skeletal musclePublication . Roman, William; Martins, João P.; Carvalho, Filomena A.; Voituriez, Raphael; Abella, Jasmine V. G.; Santos, Nuno C.; Cadot, Bruno; Way, Michael; Gomes, EdgarNuclear movements are important for multiple cellular functions, and are driven by polarized forces generated by motor proteins and the cytoskeleton. During skeletal myofibre formation or regeneration, nuclei move from the centre to the periphery of the myofibre for proper muscle function. Centrally located nuclei are also found in different muscle disorders. Using theoretical and experimental approaches, we demonstrate that nuclear movement to the periphery of myofibres is mediated by centripetal forces around the nucleus. These forces arise from myofibril contraction and crosslinking that 'zip' around the nucleus in combination with tight regulation of nuclear stiffness by lamin A/C. In addition, an Arp2/3 complex containing Arpc5L together with γ-actin is required to organize desmin to crosslink myofibrils for nuclear movement. Our work reveals that centripetal forces exerted by myofibrils squeeze the nucleus to the periphery of myofibres.
- N‐WASP is required for Amphiphysin‐2/BIN1‐dependent nuclear positioning and triad organization in skeletal muscle and is involved in the pathophysiology of centronuclear myopathyPublication . Falcone, Sestina; Roman, William; Hnia, Karim; Gache, Vincent; Didier, Nathalie; Lainé, Jeanne; Auradé, Frederic; Marty, Isabelle; Nishino, Ichizo; Charlet‐Berguerand, Nicolas; Romero, Norma Beatriz; Marazzi, Giovanna; Sassoon, David; Laporte, Jocelyn; Gomes, EdgarMutations in amphiphysin-2/BIN1, dynamin 2, and myotubularin are associated with centronuclear myopathy (CNM), a muscle disorder characterized by myofibers with atypical central nuclear positioning and abnormal triads. Mis-splicing of amphiphysin-2/BIN1 is also associated with myotonic dystrophy that shares histopathological hallmarks with CNM. How amphiphysin-2 orchestrates nuclear positioning and triad organization and how CNM-associated mutations lead to muscle dysfunction remains elusive. We find that N-WASP interacts with amphiphysin-2 in myofibers and that this interaction and N-WASP distribution are disrupted by amphiphysin-2 CNM mutations. We establish that N-WASP functions downstream of amphiphysin-2 to drive peripheral nuclear positioning and triad organization during myofiber formation. Peripheral nuclear positioning requires microtubule/Map7/Kif5b-dependent distribution of nuclei along the myofiber and is driven by actin and nesprins. In adult myofibers, N-WASP and amphiphysin-2 are only involved in the maintenance of triad organization but not in the maintenance of peripheral nuclear positioning. Importantly, we confirmed that N-WASP distribution is disrupted in CNM and myotonic dystrophy patients. Our results support a role for N-WASP in amphiphysin-2-dependent nuclear positioning and triad organization and in CNM and myotonic dystrophy pathophysiology.
- Nuclear positioning in skeletal musclePublication . Roman, William; Gomes, EdgarSkeletal muscle cells possess a unique cellular architecture designed to fulfill their contractile function. Muscle cells (also known as myofibers) result from the fusion of hundreds of myoblasts and grow into a fiber of several centimeters in length. Cellular structures gradually become organized during muscle development to raise a mature contractile cell. A hallmark of this singular cell architecture is the position of nuclei at the periphery of the myofiber, below the plasma membrane. Nuclei in myofibers are evenly distributed except in specialized regions like the neuromuscular or myotendinous junctions. Disruption of nuclear positioning results in hindered muscle contraction and occurs in a multitude of muscle disorders as well as in regenerative myofibers. We will explore in this review the step by step nuclear migrations during myogenesis for nuclei to reach their evenly distributed anchored position at the periphery.