Blood vessels and desmin control the positioning of nuclei in skeletal muscle fibers

Abstract

Skeletal muscle fibers contain hundreds to thousands of nuclei which lie immediately under the plasmalemma and are spaced out along the fiber, except for a small cluster of specialized nuclei at the neuromuscular junction. How the nuclei attain their positions along the fiber is not understood. Here we show that the nuclei are preferentially localized near blood vessels (BV), particularly in slow-twitch, oxidative fibers. Thus, in rat soleus muscle fibers, 81% of the nuclei appear next to BV. Lack of desmin markedly perturbs the distribution of nuclei along the fibers but does not prevent their close association with BV. Consistent with a role for desmin in the spacing of nuclei, we show that denervation affects the organization of desmin filaments as well as the distribution of nuclei. During chronic stimulation of denervated muscles, new BV form, along which muscle nuclei align themselves. We conclude that the positioning of nuclei along muscle fibers is plastic and that BV and desmin intermediate filaments each play a distinct role in the control of this positioning.

Effects of aging and gender on the spatial organization of nuclei in single human skeletal muscle cells

“…The reorganization of nuclei in aging human skeletal muscle supports the idea that the positioning of myonuclei is plastic in adult muscle (Ralston et al, 2006). The exact mechanisms regulating the positioning of myonuclei in muscle fibres remain unknown; however, there are several candidates: microtubuli, the intermediate filament desmin, as well as blood vessels have all been shown to be involved in the localization and ⁄ or anchoring of nuclei in muscle fibres (Bruusgaard et al, 2006;Ralston et al, 2006). Aggregation of myonuclei has been reported in response to long-term denervation (Viguie et al, 1997) and the ongoing denervation-reinnervation process in aging skeletal muscle (Larsson & Ansved, 1995) may accordingly play an important role for the aggregation of myonuclei observed in the old men and women in this study.…”

“…Consistent with previous observations in old muscle from mouse (Brack et al, 2005;Bruusgaard et al, 2006), an altered nuclear morphology and aggregation of nuclei into long chains were observed in both old men and women. The reorganization of nuclei in aging human skeletal muscle supports the idea that the positioning of myonuclei is plastic in adult muscle (Ralston et al, 2006). The exact mechanisms regulating the positioning of myonuclei in muscle fibres remain unknown; however, there are several candidates: microtubuli, the intermediate filament desmin, as well as blood vessels have all been shown to be involved in the localization and ⁄ or anchoring of nuclei in muscle fibres (Bruusgaard et al, 2006;Ralston et al, 2006).…”

Nuclear migration events throughout development

“…2E) (Sanes and Lichtman, 2001), whereas the remaining nuclei move to the myofiber surface so they are closely associated with blood vessels (Ralston et al, 2006). LINC components are required for localization of myonuclei under the NMJ (Grady et al, 2005;Lei et al, 2009;Zhang et al, 2007a), as is lamin A (Méjat et al, 2009).…”

“…For instance, in mice, knockouts of Sun1 and Sun2, nesprin-1 and nesprin-2, or the main muscle intermediate filament desmin lead to defects in nuclear anchorage (Fig. 2F) (Chapman et al, 2014;Lei et al, 2009;Ralston et al, 2006;Zhang et al, 2007a).…”

Growth patterns and nuclear distribution in white muscle fibers from black sea bass, Centropristis striata: evidence for the influence of diffusion

“…IM nuclei are rare and usually associated with diseases (Bruusgaard et al, 2003;Ralston et al, 2006). However, IM nuclei have also been reported in cases of extreme muscle fiber hypertrophy in humans (Kadi et al, 1999), chickens (Rosser et al, 2002) and crustaceans (Hardy et al, 2009;Hardy et al, 2010).…”