Cdc42 (white) polarizes even without a cue.


Polarizing cells must first pick a direction. The external cues that guide this choice are obvious: bud scars or mating partners for budding yeast, and chemoattractant gradients for Dictyostelium and neutrophils. But polarization still occurs, albeit in a random direction, when these cues are either removed or made uniform.Now, Roland Wedlich-Soldner, Rong Li (Harvard Medical School, Boston, MA), and a group of mathematical modelers have come up with an explanation for this intrinsic polarization in budding yeast. In wild-type situations, the intrinsic mechanism may be used to solidify the direction originally dictated by the external cue.

Normally, the bud scar acts as a site for activating Cdc42. Somehow, expression of activated Cdc42 is by itself sufficient to polarize cells. This polarization is now shown to involve the formation of a cap of Cdc42 on the plasma membrane. The cap's location is independent of any obvious cue, including bud scars, microtubule arrays, and lipid localization. The polarization does depend on transport apparatus—actin cables, a type V myosin motor, and vesicle exocytosis—and Cdc42 cofractionates with a secretory vesicle marker.

The researchers suggest that an initial stochastic grouping of Cdc42 on the plasma membrane stimulates the formation of actin cables and thus the vesicle-based delivery of more Cdc42. A similar positive feedback is seen in neutrophil chemotaxis, where lipids stimulate Rho GTPases to produce more lipids.

Thus, says Li, there are “intrinsic mechanisms [that] are sufficient to break symmetry without contributions from external cues.” Yeast cells lacking this feedback can still respond to a normal external cue, but their inefficient polarization results in secretion in both mother and daughter cells making the cells fat. ▪


Wedlich-Soldner, R., et al. 2003. Science. 10.1126/science.1080944.