Biophysical characterization of skeletal muscle-derived exosomes

Several cell types have the capacity to secrete nanometer-sized vesicles, exosomes, that contain cell-specific collections of proteins, lipids, and genetic material. Research on exosomes has been focusing primarily on the immune system and tumor cells; recently, we have shown that skeletal muscle (SkM) cells can release Alix-positive exosomes, suggesting the importance of exosomes in skeletal muscle biology. The subcellular architecture of skeletal muscle is very different from that of mononucleated cells, and it is now apparent that preserving muscle structure and function, proper myogenesis and regeneration require muscle-specific elaborations of known membrane trafficking pathways. For this reason, and on the basis of our findings, we believe that exosome biogenesis in muscle may differ with that of other mononucleated cells, being sustained by a direct budding of exosome from the plasma membrane. Since skeletal muscle is the largest organ in the body and it is now considered a secretory organ, it can be expected that essential discoveries on SkM-derived exosomes in health, disease, and regeneration will provide an important link between genetic and epigenetic impact factors. Our goal is to understand how muscle cells generate these vesicles and what their regulators are.