Phosphoinositides in chemotaxis

Abstract

Phosphatidylinositol lipids generated through the action of phosphinositide 3-kinase (PI3K) are key mediators of a wide array of biological responses. In particular, their role in the regulation of cell migration has been extensively studied and extends to amoeboid as well as mesenchymal migration. Through the emergence of fluorescent probes that target PI3K products as well as the use of specific inhibitors and knockout technologies, the spatio-temporal distribution of PI3K products in chemotaxing cells has been shown to represent a key anterior polarity signal that targets downstream effectors to actin polymerization. In addition, through intricate cross-talk networks PI3K products have been shown to regulate signals that control posterior effectors. Yet, in more complex environments or in conditions where chemoattractant gradients are steep, a variety of cell types can still chemotax in the absence of PI3K signals. Indeed, parallel signal transduction pathways have been shown to coordinately regulate cell polarity and directed movement. In this chapter, we will review the current role PI3K products play in the regulation of directed cell migration in various cell types, highlight the importance of mathematical modeling in the study of chemotaxis, and end with a brief overview of other signaling cascades known to also regulate chemotaxis.