Eukaryotic chemotaxis: Distinctions between directional sensing and polarization

Directional sensing and polarization are fundamental cellular responses that play a central role in health and disease. In this review we define each process and evaluate a series of models previously proposed to explain these phenomena. New findings show that directional sensing by G protein-coupled receptors is localized at a discrete step in the signaling pathway downstream of G protein activation but upstream of the accumulation of PIP3. Local levels of PIP3, whether triggered by chemoattractants, particle binding, or spontaneous events, determine the sites of new actin-filled projections. Robust control of the temporal and spatial levels of PIP3 is achieved by reciprocal regulation of PI3K and PTEN. These observations suggest that a local excitation-global inhibition model can account for the localization of PI3K and PTEN and thereby explain directional sensing. However, elements of other models, including positive feedback and the reaction of the cytoskeleton, must be invoked to account for polarization.