The sodium/ascorbic acid co-transporter SVCT2 distributes in a striated membrane-enriched domain at the M-band level in slow-twitch skeletal muscle fibers

Biol Res. 2024 Nov 6;57(1):79. doi: 10.1186/s40659-024-00554-6.

Abstract

Background: Vitamin C plays key roles in cellular homeostasis, functioning as a potent antioxidant and a positive regulator of cell differentiation. In skeletal muscle, the vitamin C/sodium co-transporter SVCT2 is preferentially expressed in oxidative slow fibers. SVCT2 is up-regulated during the early fusion of primary myoblasts and decreases during initial myotube growth, indicating the relevance of vitamin C uptake via SVCT2 for early skeletal muscle differentiation and fiber-type definition. However, our understanding of SVCT2 expression and function in adult skeletal muscles is still limited.

Results: In this study, we demonstrate that SVCT2 exhibits an intracellular distribution in chicken slow skeletal muscles, following a highly organized striated pattern. A similar distribution was observed in human muscle samples, chicken cultured myotubes, and isolated mouse myofibers. Immunohistochemical analyses, combined with biochemical cell fractionation experiments, reveal a strong co-localization of SVCT2 with intracellular detergent-soluble membrane fractions at the central sarcomeric M-band, where it co-solubilizes with sarcoplasmic reticulum proteins. Remarkably, electrical stimulation of cultured myofibers induces the redistribution of SVCT2 into a vesicular pattern.

Conclusions: Our results provide novel insights into the dynamic roles of SVCT2 in different intracellular compartments in response to functional demands.

Keywords: M-band; SVCT2; Sarcoplasmic reticulum; Skeletal muscle; Vitamin C.

MeSH terms

  • Animals
  • Ascorbic Acid / metabolism
  • Cells, Cultured
  • Chickens*
  • Humans
  • Immunohistochemistry
  • Mice
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Slow-Twitch* / metabolism
  • Sodium-Coupled Vitamin C Transporters* / metabolism

Substances

  • Sodium-Coupled Vitamin C Transporters
  • Ascorbic Acid