Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control

The 'inhibitor of apoptosis' (IAP) gene family, which was discovered less than a decade ago, encodes a group of structurally related proteins that, in addition to their ability to suppress apoptotic cell death, are involved in an increasing number of seemingly unrelated cellular functions. Here, we review the functional and structural properties of this fascinating group of proteins, and of several recently identified IAP-binding factors that regulate IAP function.

IAP proteins: blocking the road to death's door

Mitosis and cytokinesis are undoubtedly the most spectacular parts of the cell cycle. Errors in the choreography of these processes can lead to aneuploidy or genetic instability, fostering cell death or disease. Here, I give an overview of the many mitotic kinases that regulate cell division and the fidelity of chromosome transmission.

Mitotic kinases as regulators of cell division and its checkpoints

The cellular functions of the actin cytoskeleton require precise regulation of both the initiation of actin polymerization and the organization of the resulting filaments. The actin-related protein-2/3 (ARP2/3) complex is a central player in this regulation. A decade of study has begun to shed light on the molecular mechanisms by which this powerful machine controls the polymerization, organization and recycling of actin-filament networks, both in vitro and in the living cell.

The ARP2/3 complex: an actin nucleator comes of age

https://cbs.umn.edu/sites/cbs.umn.edu/files/public/downloads/2003-Kim.pdf

GβL, a Positive Regulator of the Rapamycin-Sensitive Pathway Required for the Nutrient-Sensitive Interaction between Raptor and mTOR

Comparative Analysis of Cytokinesis in Budding Yeast, Fission Yeast and Animal Cells

Schizosaccharomyces pombe is an excellent organism in which to study cytokinesis as it divides by medial fission using an F-actin contractile ring. To enhance our understanding of the cell division process, a large genetic screen was carried out in which 17 genetic loci essential for cytokinesis were identified, 5 of which are novel. Mutants identifying three genes, rng3(+), rng4(+), and rng5(+), were defective in organizing an actin contractile ring. Four mutants defective in septum deposition, septum initiation defective (sid)1, sid2, sid3, and sid4, were also identified and characterized. Genetic analyses revealed that the sid mutants display strong negative interactions with the previously described septation mutants cdc7-24, cdc11-123, and cdc14-118. The rng5(+), sid2(+), and sid3(+) genes were cloned and shown to encode Myo2p (a myosin heavy chain), a protein kinase related to budding yeast Dbf2p, and Spg1p, a GTP binding protein that is a member of the ras superfamily of GTPases, respectively. The ability of Spg1p to promote septum formation from any point in the cell cycle depends on the activity of Sid4p. In addition, we have characterized a phenotype that has not been described previously in cytokinesis mutants, namely the failure to reorganize actin patches to the medial region of the cell in preparation for septum formation.

https://www.genetics.org/content/genetics/149/3/1265.full.pdf

Isolation and Characterization of New Fission Yeast Cytokinesis Mutants

MUTATIONS in the Schizosaccharotnyces pombe cdc8 gene impair cytokinesis1. Here we clone cdc8+ and find that it encodes a novel tropomyosin. Gene disruption results in lethal arrest of the cell cycle, but spore germination, cell growth, DNA replication and mitosis are all unaffected. Haploid cdc8 gene disruptants are rescued by expression of a fibroblast tropomyosin complementary DNA. Immunofluorescence microscopy of wild type and cdc8 gene distruptants indicates that cdc8 tropomyosin is present in two distinct cellular distributions: in dispersed patches, and during cytokinesis as a transient medial band. Collectively these results indicate that cdc8 tropomyosin has a specialized role which, we suggest, is to form part of the F-actin contractile ring at cytokinesis. These results establish the basis for further genetic studies of cytokinesis and of contractile protein function in S. pombe.

A new tropomyosin essential for cytokinesis in the fission yeast S. pombe.

The fission yeast Schizosaccharomyces pombe divides by medial fission and, like many higher eukaryotic cells, requires the function of an F-actin contractile ring for cytokinesis. In S. pombe, a class of cdc- mutants defective for cytokinesis, but not for DNA replication, mitosis, or septum synthesis, have been identified. In this paper, we present the characterization of one of these mutants, cdc3-124. Temperature shift experiments reveal that mutants in cdc3 are incapable of forming an F-actin contractile ring. We have molecularly cloned cdc3 and used the cdc3+ genomic DNA to create a strain carrying a cdc3 null mutation by homologous recombination in vivo. Cells bearing a cdc3-null allele are inviable. They arrest the cell cycle at cytokinesis without forming a contractile ring. DNA sequence analysis of the cdc3+ gene reveals that it encodes profilin, an actin-monomer-binding protein. In light of recent studies with profilins, we propose that Cdc3-profilin plays an essential role in cytokinesis by catalyzing the formation of the F-actin contractile ring. Consistent with this proposal are our observations that Cdc3-profilin localizes to the medial region of the cell where the F-actin contractile ring forms, and that it is essential for F-actin ring formation. Cells overproducing Cdc3-profilin become elongated, dumbbell shaped, and arrest at cytokinesis without any detectable F-actin staining. This effect of Cdc3-profilin overproduction is relieved by introduction of a multicopy plasmid carrying the actin encoding gene, act1+. We attribute these effects to potential sequestration of actin monomers by profilin, when present in excess.

/pdf/the-schizosaccharomyces-pombe-cdc3-gene-encodes-a-profilin-4ytxo48bz5.pdf

The Schizosaccharomyces pombe cdc3+ gene encodes a profilin essential for cytokinesis.

A conserved molecular machinery centered on the Cdc42 GTPase regulates cell polarity in diverse organisms. Here we review findings from budding and fission yeasts that reveal both a conserved core polarity circuit and several adaptations that each organism exploits to fulfill the needs of its lifestyle. The core circuit involves positive feedback by local activation of Cdc42 to generate a cluster of concentrated GTP-Cdc42 at the membrane. Species-specific pathways regulate the timing of polarization during the cell cycle, as well as the location and number of polarity sites.

/pdf/cell-polarity-in-yeast-4rig25k45p.pdf

Mohan K. Balasubramanian

Papers

Comparative Analysis of Cytokinesis in Budding Yeast, Fission Yeast and Animal Cells

Isolation and Characterization of New Fission Yeast Cytokinesis Mutants

A new tropomyosin essential for cytokinesis in the fission yeast S. pombe.

The Schizosaccharomyces pombe cdc3+ gene encodes a profilin essential for cytokinesis.

Cell Polarity in Yeast.