Editors' ChoiceCell Migration

Organized Randomness

Science Signaling  13 Jul 2010:
Vol. 3, Issue 130, pp. ec210
DOI: 10.1126/scisignal.3130ec210

In addition to migrating toward a chemoattractant, motile cells also undergo spontaneous, random migration in the absence of an external signal. Directed migration of Dictyostelium cells to the chemoattractant cAMP depends on the generation of the phosphatidylinositol (PtdIns) lipid PIP3 and the polymerization of actin at the leading edge of the cell (the area of the cell closest to cAMP). PIP3 is generated by the kinase PI3K and is degraded by the phosphatase PTEN; polarized localization of PI3K at the leading edge and PTEN at the rear is required for directed migration. Although both enzymes are also required for random migration, how they spatiotemporally regulate PtdIns lipids in the absence of chemoattractant is unclear. Arai et al. used live microscopy to visualize PtdIns dynamics in Dictyostelium cells that expressed the PIP3-binding pleckstrin homology (PH) domain of the kinase Akt tagged with green fluorescent protein (GFP) and PTEN tagged with the red dye TMR. In the absence of cAMP, polarized domains enriched in either PH-GFP or PTEN-TMR formed spontaneously at the plasma membrane. The domains were not stationary but moved along the membrane in waves in a clockwise fashion while maintaining their polarity; inhibition of actin polymerization had no effect on the formation or movement of these domains. Knockout of the genes encoding PI3K did not prevent the generation of PTEN-TMR domains at the membrane, but they were stationary, and cell migration was reduced. In the absence of pten expression, PH-GFP domains were also stationary. From these and other data, the authors generated a reaction-diffusion mathematical model that suggests that the self-organization of PtdIns provides a mechanism to generate cell polarity from the molecular “noise” of the PtdIns signaling system.

Y. Arai, T. Shibata, S. Matsuoka, M. J. Sato, T. Yanagida, M. Ueda, Self-organization of the phosphatidylinositol lipids signaling system for random cell migration. Proc. Natl. Acad. Sci. U.S.A. 107, 12399–12404 (2010). [Abstract] [Full Text]