PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site.
Development
; 141(11): 2289-301, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24821989
ABSTRACT
Cell-cell fusion is a regulated process that requires merging of the opposing membranes and underlying cytoskeletons. However, the integration between membrane and cytoskeleton signaling during fusion is not known. Using Drosophila, we demonstrate that the membrane phosphoinositide PI(4,5)P2 is a crucial regulator of F-actin dynamics during myoblast fusion. PI(4,5)P2 is locally enriched and colocalizes spatially and temporally with the F-actin focus that defines the fusion site. PI(4,5)P2 enrichment depends on receptor engagement but is upstream or parallel to actin remodeling. Regulators of actin branching via Arp2/3 colocalize with PI(4,5)P2 in vivo and bind PI(4,5)P2 in vitro. Manipulation of PI(4,5)P2 availability leads to impaired fusion, with a reduction in the F-actin focus size and altered focus morphology. Mechanistically, the changes in the actin focus are due to a failure in the enrichment of actin regulators at the fusion site. Moreover, improper localization of these regulators hinders expansion of the fusion interface. Thus, PI(4,5)P2 enrichment at the fusion site encodes spatial and temporal information that regulates fusion progression through the localization of activators of actin polymerization.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica no Desenvolvimento
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Fosfatidilinositol 4,5-Difosfato
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Mioblastos
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Complexo 2-3 de Proteínas Relacionadas à Actina
Limite:
Animals
Idioma:
En
Revista:
Development
Assunto da revista:
BIOLOGIA
/
EMBRIOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos