Wnt/beta-catenin pathway activation and myogenic differentiation are induced by cholesterol depletion.
Myogenic differentiation is a multistep process that begins with the commitment of mononucleated precursors that withdraw from cell cycle. These myoblasts elongate while aligning to each other, guided by the recognition between their membranes. This step is followed by cell fusion and the formation of long and striated multinucleated myotubes. We have recently shown that cholesterol depletion by methyl-beta-cyclodextrin (MbetaCD) induces myogenic differentiation by enhancing myoblast recognition and fusion. Here, we further studied the signaling pathways responsible for early steps of myogenesis. As it is known that Wnt plays a role in muscle differentiation, we used the chemical MbetaCD to deplete membrane cholesterol and investigate the involvement of the Wnt/beta-catenin pathway during myogenesis. We show that cholesterol depletion promoted a significant increase in expression of beta-catenin, its nuclear translocation and activation of the Wnt pathway. Moreover, we show that the activation of the Wnt pathway after cholesterol depletion can be inhibited by the soluble protein Frzb-1. Our data suggest that membrane cholesterol is involved in Wnt/beta-catenin signaling in the early steps of myogenic differentiation.
Mermelstein
Cláudia S
CS
Laboratório de Diferenciação Muscular e Citoesqueleto, Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21949-590, Brazil. mermelstein@ufrj.br
Portilho
Débora M
DM
Mendes
Fábio A
FA
Costa
Manoel L
ML
Abreu
José Garcia
JG
D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D002642:Chick Embryo / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D051157:Frizzled Receptors / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047392:beta-Cyclodextrins / Q000494:pharmacology
D051157:Frizzled Receptors; D051153:Wnt Proteins; D051176:beta Catenin; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol