Article Addendum

A highly conserved member of the Rho family of small GTPases, Cdc42 functions as the “master regula-tor of cell polarity. ” It has been reported that for proper establishment and main-tenance of cell polarity, Cdc42 regu-lates and requires vesicle trafficking. Importantly, we recently discovered that in budding yeast, vesicle traffick-ing also controls the localization and function of Bem3, a GTPase activat-ing protein for Cdc42. Specifically, we observed that Bem3 partitioned between the plasma membrane and an internal membrane-bound compartment. This Bem3-containing compartment was present during extended periods of api-cal growth, required actin tracks for traf-ficking to polarized sites and functioned as a recycling station that was positioned at the junction of endocytic and secre-tory pathways. Strikingly, many of these features are reminiscent of the Spitzen-körper, a dynamic structure involved in polarized growth during hyphal develop-ment in several filamentous fungi. Fur-thermore, Bem3 was not merely a passive cargo but actively recruited the secretory Rab GTPase Sec4 to this Spitzenkörper-like compartment. Importantly, this function of Bem3 was independent of its GAP activity. Our work demonstrates the existence of a complementary regula-tion between Bem3, a regulator of Cdc42 signaling and Sec4, a key component of the secretory machinery. Cell polarity is fundamental for the execution of a diverse set of cellular func-tions, such as cell differentiation, prolif-eration, and migration.1-3 A plethora of polarity regulators were identified using the budding yeast Saccharomyces cerevisiae, including Cdc42 (Cell Division Cycle 42, also called the “master regulator of cell polarity”).1,2,4 A highly conserved mem-ber of the Rho family of small GTPases, Cdc42 acts as a molecular switch that alternates between a signaling-active GTP-bound form and a signaling-inactive GDP-bound form. This cycling between the 2 Cdc42 activation states is regulate