Yeast cell fusion is mediated by spatially regulated secretion

Yeast cell fusion is equivalent to fertilization. Cell fusion requires the removal of the intervening cell wall, regulated by Fus2 and other cell fusion proteins. Fus2 is an amphiphysin-like protein that forms a complex with the BAR protein Rvs161 and the highly conserved Rho-like GTPase Cdc42 at the zone of cell fusion (ZCF); however, the function of these proteins in cell fusion has been unclear. Here, we show that the Fus2-Rvs161-Cdc42 complex regulates a mating-specific secretion event to mediate cell fusion via cell wall removal. Use of fluorogen-activated protein fusions demonstrated that the secretion of cell wall remodeling enzymes Scw4 and Gas1 is dependent on Fus2, whereas the secretion of Scw10 is independent of Fus2. We found that Cdc42 is not required for secretion <i>per se</i>, but instead functions to focus Fus2 at the ZCF, thereby allowing concentrated release of cell wall remodeling enzymes. Localized secretion of cell wall remodeling enzymes would overcome cell wall repair pathways. Additionally, Prm1, required for efficient membrane fusion, colocalizes with Fus2 at the ZCF. Localization of Prm1 at the ZCF is dependent on Fus2 and Rvs161. We propose that the Fus2-regulated vesicle population includes membrane fusion proteins as well as cell wall remodeling factors.