Moe1, a conserved protein in
            <i>Schizosaccharomyces pombe</i>
            , interacts with a Ras effector, Scd1, to affect proper spindle formation

Chen, Chang Rung; Li, Ying Chun; Chen, Jing; Hou, Ming Chin; Papadaki, Piyi; Chang, Eric C.

doi:10.1073/pnas.96.2.517

Cited by 56 publications

(51 citation statements)

References 35 publications

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“…Results presented here suggest that an increase in microtubule length can cause bending at the growing ends of the cells, resulting in C-or J-shaped cells. This conclusion is supported by similar results reported for null mutants of moe1 ϩ , a component of the Ras1 signaling pathway (Chen et al, 1999), and components of the ␥-tubulin complex (Paluh et al, 2000;Vardy and Toda, 2000). The changes in cell shape manifested in the klp⌬ mutants described here occurred in genetic backgrounds and growth conditions that made the cells especially long, including several cell cycle arrest mutants and diploid strains.…”

Section: Microtubules and Cell Morphologysupporting

confidence: 77%

Two Related Kinesins,klp5⁺andklp6⁺, Foster Microtubule Disassembly and Are Required for Meiosis in Fission Yeast

West

Malmstrom

Troxell

et al. 2001

MBoC

143

175

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The kinesin superfamily of microtubule motor proteins is important in many cellular processes, including mitosis and meiosis, vesicle transport, and the establishment and maintenance of cell polarity. We have characterized two related kinesins in fission yeast, klp5 ϩ and klp6 ϩ , that are amino-terminal motors of the KIP3 subfamily. Analysis of null mutants demonstrates that neither klp5 ϩ nor klp6 ϩ , individually or together, is essential for vegetative growth, although these mutants have altered microtubule behavior. klp5⌬ and klp6⌬ are resistant to high concentrations of the microtubule poison thiabendazole and have abnormally long cytoplasmic microtubules that can curl around the ends of the cell. This phenotype is greatly enhanced in the cell cycle mutant cdc25-22, leading to a bent, asymmetric cell morphology as cells elongate during cell cycle arrest. Klp5p-GFP and Klp6p-GFP both localize to cytoplasmic microtubules throughout the cell cycle and to spindles in mitosis, but their localizations are not interdependent. During the meiotic phase of the life cycle, both of these kinesins are essential. Spore viability is low in homozygous crosses of either null mutant. Heterozygous crosses of klp5⌬ with klp6⌬ have an intermediate viability, suggesting cooperation between these proteins in meiosis.

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Section: Microtubules and Cell Morphologysupporting

confidence: 77%

Two Related Kinesins,klp5⁺andklp6⁺, Foster Microtubule Disassembly and Are Required for Meiosis in Fission Yeast

West

Malmstrom

Troxell

et al. 2001

MBoC

143

175

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“…Inactivation of this pathway affects numerous functions, the most readily observable of which is a change of cell morphology from elongated to round. In addition, we have recently identified an additional function of this pathwaynamely, the ability to interact with a conserved protein complex containing Yin6 and Moe1 to affect spindle formation and chromosome segregation (5,18,34). The scd1 null (scd1⌬) mutants are also sterile, but this sterility does not seem to result from abnormalities in mating pheromone signaling (4).…”

mentioning

confidence: 99%

Two Ras Pathways in Fission Yeast Are Differentially Regulated by Two Ras Guanine Nucleotide Exchange Factors

Papadaki

Pizon

Onken

et al. 2002

Molecular and Cellular Biology

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How a given Ras prreotein coordinates multiple signaling inputs and outputs is a fundamental issue of signaling specificity. Schizosaccharomyces pombe contains one Ras, Ras1, that has two distinct outputs. Ras1 activates Scd1, a presumptive guanine nucleotide exchange factor (GEF) for Cdc42, to control morphogenesis and chromosome segregation, and Byr2, a component of a mitogen-activated protein kinase cascade, to control mating. So far there is only one established Ras1 GEF, Ste6. Paradoxically, ste6 null (ste6⌬) mutants are sterile but normal in cell morphology. This suggests that Ste6 specifically activates the Ras1-Byr2 pathway and that there is another GEF capable of activating the Scd1 pathway. We thereby characterized a potential GEF, Efc25. Genetic data place Efc25 upstream of the Ras1-Scd1, but not the Ras1-Byr2, pathway. Like ras1⌬ and scd1⌬, efc25⌬ is synthetically lethal with a deletion in tea1, a critical element for cell polarity control. Using truncated proteins, we showed that the C-terminal GEF domain of Efc25 is essential for function and regulated by the N terminus. We conclude that Efc25 acts as a Ras1 GEF specific for the Scd1 pathway. While ste6 expression is induced during mating, efc25 expression is constitutive. Moreover, Efc25 overexpression renders cells hyperelongated and sterile; the latter can be rescued by activated Ras1. This suggests that Efc25 can recruit Ras1 to selectively activate Scd1 at the expense of Byr2. Reciprocally, Ste6 overexpression can block Scd1 activation. We propose that external signals can partly segregate two Ras1 pathways by modulating GEF expression and that GEFs can influence how Ras is coupled to specific effectors.Ras G proteins act as molecular switches for signal transduction pathways that are important for cell proliferation, differentiation, cell death, and organization of the cytoskeleton (reviewed in reference 29). In humans, there are three RAS genes (H-, K-, and N-RAS) which encode four Ras proteins with more than 90% identity in amino acid sequence. The biochemical properties of these Ras proteins are very similar and straightforward. Ras can bind either GTP or GDP. In the resting state of the cell, Ras is primarily GDP bound and inactive. In response to signals, Ras switches to the active GTP-bound state, a process catalyzed by guanine nucleotide exchange factors (GEFs). Activated Ras stimulates effector proteins to turn on downstream pathways. How a given Ras protein functions in the cell, however, is anything but straightforward. By one count, there are at least three Ras effectors (Raf, phosphatidylinositol 3-kinase, and Ral GDS; reviewed in reference 29) and three families of GEFs containing at least five members (Sos1, Sos2, GRF1/Cdc25Mm, GRF2, and GRP [2]). Under in vitro conditions, most known Ras effectors and GEFs can frequently interact with more than one Ras protein, but how they actually match up with one another in the cell is poorly understood.We use the fission yeast Schizosaccharomyces pombe as a genetic model organism to study ...

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“…Null alleles of byr4 + , which encodes a Ras1-interacting component, induce multiple rounds of septation, and overexpression of the gene inhibits cytokinesis (Song et al, 1996). Some of these signaling components have been shown to be responsible for the organization of the cytoskeleton, e.g., disruption of ras1 + , ral1 + /scd1 + , and moe1 + causes abnormalities in microtubule organization (Pichová et al, 1995;Chen et al, 1999). Temperaturesensitive orb6 mutants become spherical with disoriented microtubule arrays, and randomized actin patches are observed at the restrictive temperature (Verde et al, 1995(Verde et al, , 1998.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a fission yeast mutant which displays defects in cell wall integrity and cytokinesis.

et al. 2001

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Moe1, a conserved protein in Schizosaccharomyces pombe , interacts with a Ras effector, Scd1, to affect proper spindle formation

Cited by 56 publications

References 35 publications

Two Related Kinesins,klp5⁺andklp6⁺, Foster Microtubule Disassembly and Are Required for Meiosis in Fission Yeast

Two Related Kinesins,klp5⁺andklp6⁺, Foster Microtubule Disassembly and Are Required for Meiosis in Fission Yeast

Two Ras Pathways in Fission Yeast Are Differentially Regulated by Two Ras Guanine Nucleotide Exchange Factors

Characterization of a fission yeast mutant which displays defects in cell wall integrity and cytokinesis.

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Moe1, a conserved protein in Schizosaccharomyces pombe , interacts with a Ras effector, Scd1, to affect proper spindle formation

Cited by 56 publications

References 35 publications

Two Related Kinesins,klp5+andklp6+, Foster Microtubule Disassembly and Are Required for Meiosis in Fission Yeast

Two Related Kinesins,klp5+andklp6+, Foster Microtubule Disassembly and Are Required for Meiosis in Fission Yeast

Two Ras Pathways in Fission Yeast Are Differentially Regulated by Two Ras Guanine Nucleotide Exchange Factors

Characterization of a fission yeast mutant which displays defects in cell wall integrity and cytokinesis.

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Resources

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Two Related Kinesins,klp5⁺andklp6⁺, Foster Microtubule Disassembly and Are Required for Meiosis in Fission Yeast

Two Related Kinesins,klp5⁺andklp6⁺, Foster Microtubule Disassembly and Are Required for Meiosis in Fission Yeast