Triggering Actin Comets Versus Membrane Ruffles: Distinctive Effects of Phosphoinositides on Actin Reorganization

Sci. Signal., 13 December 2011
Vol. 4, Issue 203, p. ra87
DOI: 10.1126/scisignal.2002033

Triggering Actin Comets Versus Membrane Ruffles: Distinctive Effects of Phosphoinositides on Actin Reorganization

  1. Tasuku Ueno1,*,
  2. Björn H. Falkenburger2,,
  3. Christopher Pohlmeyer1, and
  4. Takanari Inoue1,
  1. 1Department of Cell Biology, Center for Cell Dynamics, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  2. 2Department of Physiology and Biophysics, School of Medicine, University of Washington, Seattle, WA 98195, USA.
  1. To whom correspondence should be addressed. E-mail: jctinoue{at}jhmi.edu
  • * Present address: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.

  • Present address: Department of Neurology, RWTH Aachen University, 52074 Aachen, Germany.

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)P2]. First, using a membrane-recruitable form of PI(4)P 5-kinase, we increased PI(4,5)P2 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)P2 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)P2 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.

  • Received March 22, 2011.
  • Accepted November 22, 2011.

Citation:

T. Ueno, B. H. Falkenburger, C. Pohlmeyer, and T. Inoue, Triggering Actin Comets Versus Membrane Ruffles: Distinctive Effects of Phosphoinositides on Actin Reorganization. Sci. Signal. 4, ra87 (2011).

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