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• W1628161767 endingPage "e1005381" @default.
• W1628161767 startingPage "e1005381" @default.
• W1628161767 abstract "The formation of multinucleated muscle cells through cell-cell fusion is a conserved process from fruit flies to humans. Numerous studies have shown the importance of Arp2/3, its regulators, and branched actin for the formation of an actin structure, the F-actin focus, at the fusion site. This F-actin focus forms the core of an invasive podosome-like structure that is required for myoblast fusion. In this study, we find that the formin Diaphanous (Dia), which nucleates and facilitates the elongation of actin filaments, is essential for Drosophila myoblast fusion. Following cell recognition and adhesion, Dia is enriched at the myoblast fusion site, concomitant with, and having the same dynamics as, the F-actin focus. Through analysis of Dia loss-of-function conditions using mutant alleles but particularly a dominant negative Dia transgene, we demonstrate that reduction in Dia activity in myoblasts leads to a fusion block. Significantly, no actin focus is detected, and neither branched actin regulators, SCAR or WASp, accumulate at the fusion site when Dia levels are reduced. Expression of constitutively active Dia also causes a fusion block that is associated with an increase in highly dynamic filopodia, altered actin turnover rates and F-actin distribution, and mislocalization of SCAR and WASp at the fusion site. Together our data indicate that Dia plays two roles during invasive podosome formation at the fusion site: it dictates the level of linear F-actin polymerization, and it is required for appropriate branched actin polymerization via localization of SCAR and WASp. These studies provide new insight to the mechanisms of cell-cell fusion, the relationship between different regulators of actin polymerization, and invasive podosome formation that occurs in normal development and in disease." @default.
• W1628161767 created "2016-06-24" @default.
• W1628161767 creator A5027388608 @default.
• W1628161767 creator A5062270496 @default.
• W1628161767 creator A5079860834 @default.
• W1628161767 date "2015-08-21" @default.
• W1628161767 modified "2023-10-16" @default.
• W1628161767 title "The Formin Diaphanous Regulates Myoblast Fusion through Actin Polymerization and Arp2/3 Regulation" @default.
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• W1628161767 doi "https://doi.org/10.1371/journal.pgen.1005381" @default.
• W1628161767 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4546610" @default.
• W1628161767 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26295716" @default.

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