Novel regulation of mitotic exit by the Cdc42 effectors Gic1 and Gic2

Höfken, Thomas; Schiebel, Elmar

doi:10.1083/jcb.200309080

Cited by 43 publications

(39 citation statements)

References 51 publications

(129 reference statements)

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“…Here, we show that deletion of RDI1 suppresses the mitotic exit defect of ⌬lte1 cells at low temperatures, possibly due to Cdc42 activation. Cdc42 regulates exit from mitosis via at least three independent pathways involving the Cdc42 effectors Cla4, Ste20, and Gic1 (Figure 2A) (Hö fken and Schiebel, 2002;Jensen et al, 2002;Seshan et al, 2002;Hö fken and Schiebel, 2004). Previously, we could demonstrate that a temperature-sensitive allele of the Cdc42 GEF CDC24 in a ⌬lte1 background is lethal at all temperatures (Hö fken and Schiebel, 2002).…”

Section: Functions Of Rdi1mentioning

confidence: 99%

“…Cdc42 and its effectors Ste20, Cla4, and Gic1 promote exit from mitosis via at least three independent mechanisms (Hö fken and Schiebel, 2002; Jensen et al, 2002;Seshan et al, 2002;Hö fken and Schiebel, 2004;Bosl and Li 2005) (Figure 2A). The small GTPase Tem1 and its putative GEF Lte1 are the most upstream components of the mitotic exit network, the signaling cascade that controls exit from mitosis (Bosl and Li, 2005).…”

Section: Rdi1 Has a Role In Pseudohyphal Growth And Mitotic Exitmentioning

confidence: 99%

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The Rho GDI Rdi1 Regulates Rho GTPases by Distinct Mechanisms

Tiedje

Sakwa

Just

et al. 2008

MBoC

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The small guanosine triphosphate (GTP)-binding proteins of the Rho family are implicated in various cell functions, including establishment and maintenance of cell polarity. Activity of Rho guanosine triphosphatases (GTPases) is not only regulated by guanine nucleotide exchange factors and GTPase-activating proteins but also by guanine nucleotide dissociation inhibitors (GDIs). These proteins have the ability to extract Rho proteins from membranes and keep them in an inactive cytosolic complex. Here, we show that Rdi1, the sole Rho GDI of the yeast Saccharomyces cerevisiae, contributes to pseudohyphal growth and mitotic exit. Rdi1 interacts only with Cdc42, Rho1, and Rho4, and it regulates these Rho GTPases by distinct mechanisms. Binding between Rdi1 and Cdc42 as well as Rho1 is modulated by the Cdc42 effector and p21-activated kinase Cla4. After membrane extraction mediated by Rdi1, Rho4 is degraded by a novel mechanism, which includes the glycogen synthase kinase 3␤ homologue Ygk3, vacuolar proteases, and the proteasome. Together, these results indicate that Rdi1 uses distinct modes of regulation for different Rho GTPases. INTRODUCTIONSmall guanosine triphosphatases (GTPases) of the Rho family control fundamental processes of cell biology common to all eukaryotes, such as morphogenesis, polarity, movement, and cell division (Jaffe and Hall, 2005). In the budding yeast Saccharomyces cerevisiae, which encodes six Rho GTPases (Cdc42 and Rho1 to Rho5), these proteins play a pivotal role in the establishment of cell polarity (Park and Bi, 2007). Budding yeast cells undergo polarized growth during various phases of their life cycle, including budding during vegetative growth, mating between haploid cells of opposite mating types, and filamentous growth upon nutrient limitation. Although Cdc42 and Rho1 are well characterized, little is known about the other Rho proteins. Membrane association of Rho-type GTPases is essential for their function, and it depends on a C-terminal prenyl moiety and an adjacent polybasic region. Cdc42 localizes to internal membranes and the entire plasma membrane, where it clusters at sites of polarized growth, including the tips of mating projections, incipient bud sites, the tips and sides of growing buds, and the bud neck region of large-budded cells (Ziman et al., 1993;Richman et al., 2002). In addition to membranebound Cdc42, a cytoplasmic pool has been found (Ziman et al., 1993). Similar to Cdc42, Rho1 has been shown to localize at sites of polarized growth .Like other regulatory GTPases, they act as molecular switches, cycling between an active guanosine triphosphate (GTP)-bound state and an inactive guanosine diphosphate (GDP)-bound state. This activity is highly regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). The exchange of GDP to GTP, and thus the activation of Cdc42, is catalyzed by GEFs. In the active GTP-bound state, Rho GTPases perform their regulatory function through a conformation-specific interaction with effector proteins. G...

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Section: Functions Of Rdi1mentioning

confidence: 99%

Section: Rdi1 Has a Role In Pseudohyphal Growth And Mitotic Exitmentioning

confidence: 99%

The Rho GDI Rdi1 Regulates Rho GTPases by Distinct Mechanisms

Tiedje

Sakwa

Just

et al. 2008

MBoC

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“…Although the exact mechanism is unclear in either process, this might be another example of flexible regulatory linkages between conserved core elements to implement specific morphogenetic responses. In addition to the role in bud formation, the Gic proteins, as well as the PAKs, also play a role in mitotic exit control, which senses spindle orientation relative to the axis of polarity [110][111][112].…”

Section: Regulatory Linkages Downstream Of Cdc42mentioning

confidence: 99%

Yeast and fungal morphogenesis from an evolutionary perspective

Wedlich‐Söldner

2008

Seminars in Cell & Developmental Biology

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Cellular morphogenesis is a complex process and molecular studies in the last few decades have amassed a large amount of information that is difficult to grasp in any completeness. Fungal systems, in particular the budding and fission yeasts, have been important players in unravelling the basic structural and regulatory elements involved in a wide array of cellular processes. In this article, we address the design principles underlying the various processes of yeast and fungal morphogenesis. We attempt to explain the apparent molecular complexity from the perspective of the evolutionary theory of "facilitated variation". Following a summary of some of the most studied morphogenetic phenomena, we discuss, using recent examples, the underlying core processes and their associated "weak" regulatory linkages that bring about variation in morphogenetic phenotypes.

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“…Two protein kinases were isolated-Mck1, which has a role in chromosome segregation, and Rck2, which has a role in the osmotic stress response pathway (Neigeborn and Mitchell, 1991;Shero and Hieter, 1991;Bilsland-Marchesan et al, 2000). We identified Gic1, which has roles in cell polarity and mitotic exit (Brown et al, 1997;Chen et al, 1997;Hofken and Schiebel, 2004). Finally, we identified the Hcm1 transcription factor, which has also been isolated in a variety of synthetic lethal screens pertaining to the cell division cycle and chromosome segregation (Zhu and Davis, 1998;Horak et al, 2002;Sarin et al, 2004;Montpetit et al, 2005;Daniel et al, 2006).…”

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confidence: 99%

Spc24 and Stu2 Promote Spindle Integrity When DNA Replication Is Stalled

McQueen

Cuschieri²,

Vogel

et al. 2007

MBoC

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The kinetochore, a protein complex that links chromosomes to microtubules (MTs), is required to prevent spindle expansion during S phase in budding yeast, but the mechanism of how the kinetochore maintains integrity of the bipolar spindle before mitosis is not well understood. Here, we demonstrate that a mutation of Spc24, a component of the conserved Ndc80 kinetochore complex, causes lethality when cells are exposed to the DNA replication inhibitor hydroxyurea (HU) due to premature spindle expansion and segregation of incompletely replicated DNA. Overexpression of Stu1, a CLASP-related MT-associated protein or a truncated form of the XMAP215 orthologue Stu2 rescues spc24-9 HU lethality and prevents spindle expansion. Truncated Stu2 likely acts in a dominant-negative manner, because overexpression of full-length STU2 does not rescue spc24-9 HU lethality, and spindle expansion in spc24-9 HU-treated cells requires active Stu2. Stu1 and Stu2 localize to the kinetochore early in the cell cycle and Stu2 kinetochore localization depends on Spc24. We propose that mislocalization of Stu2 results in premature spindle expansion in S phase stalled spc24-9 mutants. Identifying factors that restrain spindle expansion upon inhibition of DNA replication is likely applicable to the mechanism by which spindle elongation is regulated during a normal cell cycle. INTRODUCTIONPreserving the integrity of the genome is a fundamental requirement for eukaryotic cell viability. DNA replication must be completed before segregation of the chromosomes to prevent the transmission of partially replicated chromosomes to daughter cells. In the budding yeast Saccharomyces cerevisiae, cells undergo a closed mitosis and the microtubule (MT) organizing centers, or spindle pole bodies (SPBs), are imbedded in the nuclear envelope. SPB duplication begins at the end of anaphase and spindle formation begins during S phase when duplicated SPBs separate from each other (Adams and Kilmartin, 1999;Jaspersen and Winey, 2004). Because chromosomes remain attached to kinetochore MTs throughout the cell cycle, spindle expansion must be restrained until all 16 chromosomes have duplicated and kinetochores on sister chromatids have formed bipolar MT attachments. When DNA replication is stalled by hydroxyurea (HU) treatment, cells arrest with a large bud, an undivided nucleus positioned at the mother-bud neck and a short bipolar spindle (Allen et al., 1994). Maintaining a short spindle is crucial for cell survival during HU-induced arrest, which activates the DNA replication checkpoint effectors Mec1 and Rad53 (Kolodner et al., 2002). When mec1 and rad53 mutants are treated with HU, the DNA replication checkpoint is not activated, and, as a result, replication forks are not stabilized, the spindle expands, and unequal division of incompletely replicated nuclear material occurs-all of these events contribute to cell lethality (Allen et al., 1994;Weinert et al., 1994;Lopes et al., 2001).In human cells, stalled replication forks activate the ataxia telangiectasia mutat...

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Novel regulation of mitotic exit by the Cdc42 effectors Gic1 and Gic2

Cited by 43 publications

References 51 publications

The Rho GDI Rdi1 Regulates Rho GTPases by Distinct Mechanisms

The Rho GDI Rdi1 Regulates Rho GTPases by Distinct Mechanisms

Yeast and fungal morphogenesis from an evolutionary perspective

Spc24 and Stu2 Promote Spindle Integrity When DNA Replication Is Stalled

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