title: Triggering actin comets versus membrane ruffles: distinctive effects of phosphoinositides on actin reorganization.
abstract: A limited set of phosphoinositide membrane lipids regulate diverse cellular functions including proliferation, differentiation, and migration. We developed two techniques based on rapamycin-induced protein dimerization to rapidly change the concentration of plasma membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)]. First, using a membrane-recruitable form of PI(4)P 5-kinase, we increased PI(4,5)P(2) synthesis from phosphatidylinositol 4-phosphate [PI(4)P] and found that COS-7, HeLa, and human embryonic kidney 293 cells formed bundles of motile actin filaments known as actin comets. In contrast, a second technique that increased the concentration of PI(4,5)P(2) without consuming PI(4)P induced membrane ruffles. These distinct phenotypes were mediated by dynamin-mediated vesicular trafficking and mutually inhibitory crosstalk between the small guanosine triphosphatases Rac and RhoA. Our results indicate that the effect of PI(4,5)P(2) on actin reorganization depends on the abundance of other phosphoinositides, such as PI(4)P. Thus, combinatorial regulation of phosphoinositide concentrations may contribute to the diversity of phosphoinositide functions.
authors.affiliation: Department of Cell Biology, Center for Cell Dynamics, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Ueno
authors.forename: Björn H
authors.initials: BH
authors.lastname: Falkenburger
authors.forename: Christopher
authors.initials: C
authors.lastname: Pohlmeyer
authors.forename: Takanari
authors.initials: T
authors.lastname: Inoue
mesh_terms: D000199:Actins / Q000737:chemistry*; D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D041681:NIH 3T3 Cells; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D020741:rho GTP-Binding Proteins