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Triggering actin comets versus membrane ruffles: distinctive effects of phosphoinositides on actin reorganization.

Authors
  • Ueno, Tasuku
  • Falkenburger, Björn H
  • Pohlmeyer, Christopher
  • Inoue, Takanari
Type
Published Article
Journal
Science Signaling
Publisher
American Association for the Advancement of Science (AAAS)
Publication Date
Jan 01, 2011
Volume
4
Issue
203
Identifiers
DOI: 10.1126/scisignal.2002033
PMID: 22169478
Source
Medline
License
Unknown

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.

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