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pubmed:abstractText |
IL-15 receptor ? (IL-15R?) is a component of the heterotrimeric plasma membrane receptor for the pleiotropic cytokine IL-15. However, IL-15R? is not merely an IL-15 receptor subunit, as mice lacking either IL-15 or IL-15R? have unique phenotypes. IL-15 and IL-15R? have been implicated in muscle phenotypes, but a role in muscle physiology has not been defined. Here, we have shown that loss of IL-15R? induces a functional oxidative shift in fast muscles, substantially increasing fatigue resistance and exercise capacity. IL-15R?-knockout (IL-15R?-KO) mice ran greater distances and had greater ambulatory activity than controls. Fast muscles displayed fatigue resistance and a slower contractile phenotype. The molecular signature of these muscles included altered markers of mitochondrial biogenesis and calcium homeostasis. Morphologically, fast muscles had a greater number of muscle fibers, smaller fiber areas, and a greater ratio of nuclei to fiber area. The alterations of physiological properties and increased resistance to fatigue in fast muscles are consistent with a shift toward a slower, more oxidative phenotype. Consistent with a conserved functional role in humans, a genetic association was found between a SNP in the IL15RA gene and endurance in athletes stratified by sport. Therefore, we propose that IL-15R? has a role in defining the phenotype of fast skeletal muscles in vivo.
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