page 583) place Rho GTPases at the top of this polarization ladder.In the past, Rho GTPases were thought to polarize secretion by recruiting the exocyst. This hypothesis stemmed mainly from the fact that exocyst proteins bind directly to the GTPases.
Roumanie and colleagues now show that the exocyst is polarized even when its interaction with Rho is impaired. They identified yeast strains with Rho GTPase mutations that impair exocytosis at the bud but not the localization of the important players. The exocyst is therefore at the bud site, yet not fully active.
Secretion defects were rescued by GTP-bound forms of Rho, but rescue did not require GTP hydrolysis. Based on other Rho functions (such as Arp2/3 activation), the authors suggest that RhoGTP induces conformational changes in the exocyst that relieve autoinhibitory interactions.
Exocyst localization may simply be a readout rather than a determinant of polarized secretion. As a first step, a change in location of active Rho could rapidly activate exocytosis at a new site, as exocyst components are found at low levels throughout the cell. This should result in a positive feedback effect that concentrates exocyst components at that site, as those components (which are known to be present on exocytic vesicles) are pulled off distant membranes and inserted at the exocytic site.