Cdc42p and Fus2p act together late in yeast cell fusion

Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Molecular biology of the cell (Impact Factor: 4.47). 02/2012; 23(7):1208-18. DOI: 10.1091/mbc.E11-08-0723
Source: PubMed


Cell fusion is the key event of fertilization that gives rise to the diploid zygote and is a nearly universal aspect of eukaryotic biology. In the yeast Saccharomyces cerevisiae, several mutants have been identified that are defective for cell fusion, and yet the molecular mechanism of this process remains obscure. One obstacle has been that genetic screens have mainly focused on mating-specific factors, whereas the process likely involves housekeeping proteins as well. Here we implicate Cdc42p, an essential protein with roles in multiple aspects of morphogenesis, as a core component of the yeast cell fusion pathway. We identify a point mutant in the Rho-insert domain of CDC42, called cdc42-138, which is specifically defective in cell fusion. The cell fusion defect is not a secondary consequence of ineffective signaling or polarization. Genetic and morphological data show that Cdc42p acts at a late stage in cell fusion in concert with a key cell fusion regulator, Fus2p, which contains a Dbl-homology domain. We find that Fus2p binds specifically with activated Cdc42p, and binding is blocked by the cdc42-138 mutation. Thus, in addition to signaling and morphogenetic roles in mating, Cdc42p plays a role late in cell fusion via activation of Fus2p.


Available from: Casey Ydenberg, May 14, 2014
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    • "For this, both a fusion-specific transmembrane protein Fus1 (unrelated to its fission yeast formin Fus1 namesake) as well as Spa2, a formin-binding factor, are required (Gammie et al., 1998). Further, the Cdc42-interacting protein Fus2, also necessary for cell wall digestion, displays a focused localization at the fusion site, which relies on both Fus1-and actin-based transport (Paterson et al., 2008; Sheltzer and Rose, 2009; Ydenberg et al., 2012). The precise role of the actin cytoskeleton has not been defined, though the formin Bni1, tropomyosin Tpm1, and type V myosin Myo2 are all required for cell fusion (Liu and Bretscher, 1992; Dorer et al., 1997; Sheltzer and Rose, 2009). "
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    • "It functions late during fusion, blocking pairs with vesicles tightly clustered at the zone of fusion [110]. Similar phenotype is observed for a specific cdc42 allele, which displays defects only in cell fusion [105]. Fus2, which contains a putative Rho-GEF domain, in fact binds GTP-Cdc42 directly, suggesting it acts as a Cdc42 effector for fusion [105]. "
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