LAUSR

Smk1 is a meiosis-specific MAPK in yeast that controls spore differentiation. It is activated by a MAPK binding-protein, Ssp2, upon completion of the meiotic divisions. The activation of Smk1 by Ssp2 is positively regulated by a meiosis-specific co-activator of the Anaphase Promoting Complex (APC/C) E3 ubiquitin ligase, Ama1. Here, we identify Isc10 as an inhibitor that links APC/CAma1 to Smk1 activation. Isc10 and Smk1 form an inhibited complex during MI. Ssp2 is produced later in the program and it forms a ternary complex with Isc10 and Smk1 during MII that is poised for activation. Upon completion of MII, Isc10 is ubiquitylated and degraded in an AMA1-dependent manner, thereby triggering the activation of Smk1 by Ssp2. Mutations that cause Ssp2 to be produced before MII, or isc10Δ, modestly reduced the efficiency of spore differentiation while spores were nearly absent in the double mutant. These findings define a pathway that couples spore differentiation to the G0-like phase of the cell-cycle.