Interplay between microtubule interactome, myonuclei mechanotransduction, and positioning in myopathies

Figures

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  Figure 1.. Myonuclei movements and interplay with microtubules interactome along myofiber formation. (a) Scheme representing different steps of myofiber formation and maturation. (b) Representative images of in vitro murine primary myoblast/myocyte/myotube and isolated myofiber from Tibialis Anterior muscle of a 4 months mouse. Myonuclei appear in magenta, cyan, or blue and microtubules in gray. Scale bar: 10 µm.

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  Figure 2.. Myonucleus interacts with its environment to ensure its anchoring at the periphery of myofibers. Various interactions site between myonuclei membrane and the myofibers are supported by the MT network. (a) Sub-sarcolemma site. Costameres are specialized structures linking the sarcolemma with the myofibrils, formed by the dystroglycan complex (DGC) and integrin complex (α and β) forming costameres. The β unit of DGC (β-DG) interacts with dystrophin, promoting the formation of dystrophin-associated protein complex (DAPC), which forms the base of the scaffold between with extracellular matrix (ECM) and cytoskeleton. On one hand, β-DG is linked with collagen IV from basal lamina through laminin-1,2-nidogen-perlecan. On the other hand, DAPC interacts with three cytoskeleton filaments: β-DG interacts with desmin through plectin, dystrophin interacts with γ-actin, and indirectly with MTs through MACF1. In parallel, α-integrin is linked with collagen IV with the same partners for DAPC. β-integrin is associated with γ-actin by Talin or Talin-Vinculin. The plectin interacts with β-DG and β-integrin ensuring the interplay with these two complexes with desmin. The MT polymerization is…

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  Figure 3.. Myonuclei positioning in human muscular diseases. (a) Example of transversal section of muscle biopsies from patients exhibiting myonuclei mispositioned (orange arrow) or centralized (white arrow) in selected muscular diseases provided by the HCL-Lyon (Hematoxylin-Eosin (HE) staining). Diseases are identified by OMIM code: https://www.omim.org/ CMT2L: Charcot–Marie–Tooth type 2 L, CNM: CentroNuclear myopathy, DM2: myotonic Dystrophy 2, LGMDR1: limb-Girdle muscular Dystrophy 1, DMD: Duchenne muscular Dystrophy, MFM1: MyoFibrillar 1 (b) Pie chart representing the proportion of diseases listed in Table 1 regarding myonuclei positioning. (c) Scheme representing the myonuclei localization in muscle fiber: 1) peripheral myonuclei, 2) mispositioned myonuclei, and 3) centralized nuclei.