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 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.
authors.affiliation: Program in Developmental Biology, Sloan Kettering Institute, New York, NY 10065, USA.
authors.forename: Ingo
authors.initials: I
authors.lastname: Bothe
authors.affiliation: Graduate Program in Physiology, Biophysics & Systems Biology, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA.
authors.forename: Su
authors.initials: S
authors.lastname: Deng
authors.affiliation: Program in Developmental Biology, Sloan Kettering Institute, New York, NY 10065, USA Graduate Program in Physiology, Biophysics & Systems Biology, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA m-baylies@ski.mskcc.org.
authors.forename: Mary
authors.initials: M
authors.lastname: Baylies
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004331:Drosophila melanogaster; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009154:Mutation; D032446:Myoblasts / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000737:chemistry*; D010743:Phospholipids / Q000378:metabolism; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010743:Phospholipids; D020744:rac GTP-Binding Proteins
keywords: Actin regulation; Arp2/3 regulators; Drosophila; Myoblast fusion; PI(4,5)P2; PtdIns(4,5)P2