The Saccharomyces cerevisiae Mob2p–Cbk1p kinase complex promotes polarized growth and acts with the mitotic exit network to facilitate daughter cell–specific localization of Ace2p transcription factor

Abstract

The Saccharomyces cerevisiae mitotic exit network (MEN) is a conserved signaling network that coordinates events associated with the M to G1 transition. We investigated the function of two S. cerevisiae proteins related to the MEN proteins Mob1p and Dbf2p kinase. Previous work indicates that cells lacking the Dbf2p-related protein Cbk1p fail to sustain polarized growth during early bud morphogenesis and mating projection formation (Bidlingmaier, S., E.L. Weiss, C. Seidel, D.G. Drubin, and M. Snyder. 2001. Mol. Cell. Biol. 21:2449–2462). Cbk1p is also required for Ace2p-dependent transcription of genes involved in mother/daughter separation after cytokinesis. Here we show that the Mob1p-related protein Mob2p physically associates with Cbk1p kinase throughout the cell cycle and is required for full Cbk1p kinase activity, which is periodically activated during polarized growth and mitosis. Both Mob2p and Cbk1p localize interdependently to the bud cortex during polarized growth and to the bud neck and daughter cell nucleus during late mitosis. We found that Ace2p is restricted to daughter cell nuclei via a novel mechanism requiring Mob2p, Cbk1p, and a functional nuclear export pathway. Furthermore, nuclear localization of Mob2p and Ace2p does not occur in mob1–77 or cdc14–1 mutants, which are defective in MEN signaling, even when cell cycle arrest is bypassed. Collectively, these data indicate that Mob2p–Cbk1p functions to (a) maintain polarized cell growth, (b) prevent the nuclear export of Ace2p from the daughter cell nucleus after mitotic exit, and (c) coordinate Ace2p-dependent transcription with MEN activation. These findings may implicate related proteins in linking the regulation of cell morphology and cell cycle transitions with cell fate determination and development.

DrosophilaMob Family Proteins Interact with the Related Tricornered (Trc) and Warts (Wts) Kinases

“…Evidence for a direct physical interaction has been reported for Ndr and Mob family members from yeast, flies and mammals (Colman-Lerner et al, 2001;Mah et al, 2001;Weiss et al, 2002;Hou et al, 2003;Bichsel et al, 2004;Lai et al, 2005). Previous yeast two-hybrid experiments showed evidence for a physical interaction between Trc and Mats (Giot et al, 2003) and Mats and Wts (Lai et al, 2005).…”

“…The S. cerevisiae Cbk1 and Mob2 proteins are known to interact physically as do the S. pombe homologues (Orb6 and Mob2; Weiss et al, 2002;Hou et al, 2003). In addition the related Dbf2 and Mob1 proteins of S. cerevisiae also interact physically (Komarnitsky et al, 1998).…”

“…The Mob2 protein of yeast has been shown to bind to Cbk1 and be essential for Cbk1 kinase activity (Weiss et al, 2002). In vivo Mob2 is required along with Cbk1 for both mother/daughter separation after cytokinesis and the maintenance of polarized cell growth (Weiss et al, 2002). Furthermore, Mob2 and Cbk1 show interdependent localization (Nelson et al, 2003).…”

“…This suggests that homologues of other members of the RAM pathway in S. cerevisiae will also play similar roles in higher eukaryotes. The Mob2 protein of yeast has been shown to bind to Cbk1 and be essential for Cbk1 kinase activity (Weiss et al, 2002). In vivo Mob2 is required along with Cbk1 for both mother/daughter separation after cytokinesis and the maintenance of polarized cell growth (Weiss et al, 2002).…”

Yeast and fungal morphogenesis from an evolutionary perspective

“…After nuclear division, cytokinesis occurs through constriction of an actomyosin ring at the bud neck coupled with formation of the primary septum catalyzed by chitin synthase II [22,23]. Cell separation is accomplished through a cohort of cell wall remodelling enzymes [24,25]. The position of an incipient bud site on the cortex is specified through a process termed "bud site selection" and depends on the previous sites of cell division known as bud scars (on mother cells) or birth scars (on daughter cells) [26].…”