Yeast chemotropism: A paradigm shift in chemical gradient sensing

Abstract

The ability of cells to direct their movement and growth in response to shallow chemical gradients is essential in the life cycles of all eukaryotic organisms. The signaling mechanisms underlying directional sensing in chemotactic cells have been well studied; however, relatively little is known about how chemotropic cells interpret chemical gradients. Recent studies of chemotropism in budding and fission yeast have revealed 2 quite different mechanisms-biased wandering of the polarity complex, and differential internalization of the receptor and G protein. Each of these mechanisms has been proposed to play a key role in decoding mating pheromone gradients. Here we explore how they may work together as 2 essential components of one gradient sensing machine.

Keywords: GPCR; chemical gradient sensing; chemotropism; heterotrimeric G protein; pheromone response; yeast mating.

Figure 1.

A unified model of yeast gradient sensing. (A) Gβγ constraint of polarity complex wandering. Actin-dependent vesicle docking drives random movement of the Bem1-Cdc24-Cdc42 polarity complex along the PM, but movement of the complex is biased up the pheromone gradient by its interaction with Gβγ. Activated receptor catalyzes the release of Gβγ, which inhibits receptor phosphorylation through its interaction with the receptor kinase, and thereby differentially protects both receptor and G protein from internalization at the incipient mating projection site. (B) Gradient-induced positioning of the chemotropic site. Gβγ inhibition of receptor and G protein internalization initiates a positive feedback loop that concentrates active-unphosphorylated receptor and G protein where the external pheromone concentration is highest. Thus, actin-independent polarization of Gβγ generates a positional cue that aligns the polarity complex with the pheromone gradient prior to cellular morphogenesis.