title: Dynamic clustering and dispersion of lipid rafts contribute to fusion competence of myogenic cells.
abstract: Recent research indicates that the leading edge of lamellipodia of myogenic cells (myoblasts and myotubes) contains presumptive fusion sites, yet the mechanisms that render the plasma membrane fusion-competent remain largely unknown. Here we show that dynamic clustering and dispersion of lipid rafts contribute to both cell adhesion and plasma membrane union during myogenic cell fusion. Adhesion-complex proteins including M-cadherin, beta-catenin, and p120-catenin accumulated at the leading edge of lamellipodia, which contains the presumptive fusion sites of the plasma membrane, in a lipid raft-dependent fashion prior to cell contact. In addition, disruption of lipid rafts by cholesterol depletion directly prevented the membrane union of myogenic cell fusion. Time-lapse recording showed that lipid rafts were laterally dispersed from the center of the lamellipodia prior to membrane fusion. Adhesion proteins that had accumulated at lipid rafts were also removed from the presumptive fusion sites when lipid rafts were laterally dispersed. The resultant lipid raft- and adhesion complex-free area at the leading edge fused with the opposing plasma membrane. These results demonstrate a key role for dynamic clustering/dispersion of lipid rafts in establishing fusion-competent sites of the myogenic cell membrane, providing a novel mechanistic insight into the regulation of myogenic cell fusion.
authors.affiliation: Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Morioka, Oobu, Aichi 474-8522, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mukai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurisaki
authors.forename: Satoshi B
authors.initials: SB
authors.lastname: Sato
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Gen
authors.initials: G
authors.lastname: Kondoh
authors.forename: Naohiro
authors.initials: N
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D018929:Cell Culture Techniques / Q000379:methods; D002459:Cell Fusion / Q000379:methods; D002999:Clone Cells; D005260:Female; D005455:Fluorescent Antibody Technique; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D021962:Membrane Microdomains / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008813:Mice, Inbred ICR; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000032:analysis / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D049452:Green Fluorescent Proteins; D018995:Myosin Heavy Chains