PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site Journal Article
| Authors: | Bothe, I.; Deng, S.; Baylies, M. |
| Article Title: | PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site |
| 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 receptorengagement 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 localizationof theseregulators hindersexpansion 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. © 2014. Published by The Company of Biologists Ltd. |
| Keywords: | unclassified drug; nonhuman; protein localization; drosophila; f actin; cell adhesion; actin polymerization; actin related protein 2-3 complex; myoblast fusion; cell fusion; myoblast; myotube; muscle development; phosphatidylinositide; actin filament; priority journal; article; actin regulation; arp2/3 regulators; pi(4,5)p2; phosphatidylinositide pi(4,5)p2 |
| Journal Title: | Development |
| Volume: | 141 |
| Issue: | 11 |
| ISSN: | 0950-1991 |
| Publisher: | Company of Biologists |
| Date Published: | 2014-06-01 |
| Start Page: | 2289 |
| End Page: | 2301 |
| Language: | English |
| DOI: | 10.1242/dev.100743 |
| PROVIDER: | scopus |
| PUBMED: | 24821989 |
| PMCID: | PMC4034421 |
| DOI/URL: | |
| Notes: | Development -- Export Date: 8 July 2014 -- CODEN: DEVPE -- Source: Scopus |
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