Microtubules as Determinants of Cellular Polarity

Abstract

Most eukaryotic cells respond to developmental or environmental stimuli with a change in their polarity. Inherent in this behavior is the ability of the cell to detect the extracellular cue, to transmit a signal across a plasma membrane, and to translate the signal into molecules that can produce the requisite architecture of change. The overall response could be modulated by the expression of new genes, but since many such responses can be generated without new genetic input, this is not an essential feature of the response. We and others have been asking, in particular, how elements of the cytoskeleton, especially microtubules (MTs), contribute to the generation of cellular polarity by responding to environmental cues and transmitting the information to other cellular constituents. Unlike other signal transduction systems (e.g., growth factor activation of gene expression), the one involving MTs mediates a cellular response that reflects the spatial information provided by the original extracellular cue. Individual elements of this MT system will be described, and the possible mechanisms by which cells achieve functional polarity will be discussed. The biological system that we use in most of our studies is an in vitro wound-healing model. Fibroblasts are grown in culture until confluent, and narrow strips of cells are then scraped off the substratum. The cells at the wound edge are initially unpolarized, but in response to wounding, they become polarized with their long axis perpendicular to the wound and with an active leading edge at the portion of the cell facing the cell-free area.