title: In-depth analysis of the secretome identifies three major independent secretory pathways in differentiating human myoblasts.
abstract: Efficient muscle regeneration requires cross talk between multiple cell types via secreted signaling molecules. However, as yet there has been no comprehensive analysis of this secreted signaling network in order to understand how it regulates myogenesis in humans. Using integrated proteomic and genomic strategies, we show that human muscle cells release not only soluble secreted proteins through conventional secretory mechanisms but also complex protein and nucleic acid cargos via membrane microvesicle shedding. The soluble secretome of muscle cells contains 253 conventionally secreted signaling proteins, including 43 previously implicated in myogenesis, while others are known to modulate various cell types thus implying a much broader role for myoblasts in muscle remodeling. We also isolated and characterized two types of secreted membrane-derived vesicles: nanovesicles harboring typical exosomal features and larger, morphologically distinct, microvesicles. While they share some common features, their distinct protein and RNA cargos suggest independent functions in myogenesis. We further demonstrate that both types of microvesicles can dock and fuse with adjacent muscle cells but also deliver functional protein cargo. Thus, the intercellular signaling networks invoked during muscle differentiation and regeneration may employ conventional soluble signaling molecules acting in concert with muscle derived microvesicles delivering their cargos directly into target cells.
authors.affiliation: Université Pierre et Marie Curie, Paris 6, UM76, Institut de Myologie, Bâtiment Babinski, GH Pitié Salpêtrière, 47, bd de l'Hôpital, Paris, F-75013, France.
authors.forename: Marie-Catherine
authors.initials: MC
authors.lastname: Le Bihan
authors.forename: Anne
authors.initials: A
authors.lastname: Bigot
authors.forename: Søren Skov
authors.initials: SS
authors.lastname: Jensen
authors.forename: Jayne L
authors.initials: JL
authors.lastname: Dennis
authors.forename: Adelina
authors.initials: A
authors.lastname: Rogowska-Wrzesinska
authors.forename: Jeanne
authors.initials: J
authors.lastname: Lainé
authors.forename: Vincent
authors.initials: V
authors.lastname: Gache
authors.forename: Denis
authors.initials: D
authors.lastname: Furling
authors.forename: Ole Nørregaard
authors.initials: ON
authors.lastname: Jensen
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.forename: Gary R
authors.initials: GR
authors.lastname: Coulton
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D009124:Muscle Proteins / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism*; D055571:Secretory Pathway / Q000502:physiology*
chemical_list: D009124:Muscle Proteins; D020543:Proteome