Small GTPases use GDP/GTP alternation to actuate a variety of functional switches that are pivotal for cell dynamics. The GTPase switch is turned on by GEFs, which stimulate dissociation of the tig...

Regulation of Small GTPases by GEFs, GAPs, and GDIs

The spatial and temporal organization of molecules within a cell is critical for coordinating the many distinct activities carried out by the cell. In an increasing number of biological signaling processes, scaffold proteins have been found to play a central role in physically assembling the relevant molecular components. Although most scaffolds use a simple tethering mechanism to increase the efficiency of interaction between individual partner molecules, these proteins can also exert complex allosteric control over their partners and are themselves the target of regulation. Scaffold proteins offer a simple, flexible strategy for regulating selectivity in pathways, shaping output behaviors, and achieving new responses from preexisting signaling components. As a result, scaffold proteins have been exploited by evolution, pathogens, and cellular engineers to reshape cellular behavior.

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Scaffold Proteins: Hubs for Controlling the Flow of Cellular Information

The cyclin dependent kinase Cdk1 controls the cell cycle, which is best understood in the model organism S. cerevisiae. Research performed during the past decade has significantly improved our understanding of the molecular machinery of the cell cycle. Approximately 75 targets of Cdk1 have been identified that control critical cell cycle events, such as DNA replication and segregation, transcriptional programs and cell morphogenesis. In this review we discuss currently known targets of Cdk1 in the budding yeast S. cerevisiae and highlight the role of Cdk1 in several crucial processes including maintenance of genome stability.

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An overview of Cdk1-controlled targets and processes

Asymmetric cell division, which includes cell polarization and cytokinesis, is essential for generating cell diversity during development. The budding yeast Saccharomyces cerevisiae reproduces by asymmetric cell division, and has thus served as an attractive model for unraveling the general principles of eukaryotic cell polarization and cytokinesis. Polarity development requires G-protein signaling, cytoskeletal polarization, and exocytosis, whereas cytokinesis requires concerted actions of a contractile actomyosin ring and targeted membrane deposition. In this chapter, we discuss the mechanics and spatial control of polarity development and cytokinesis, emphasizing the key concepts, mechanisms, and emerging questions in the field.

https://www.genetics.org/content/genetics/191/2/347.full.pdf

Cell Polarization and Cytokinesis in Budding Yeast

Our understanding of endocytosis has evolved remarkably in little more than a decade. This is the result not only of advances in our knowledge of its molecular and biological workings, but also of ...

/pdf/endocytosis-and-signaling-cell-logistics-shape-the-3mbyjpcsps.pdf

Endocytosis and signaling: cell logistics shape the eukaryotic cell plan.

Symmetry-Breaking Polarization Driven by a Cdc42p GEF-PAK Complex

The role of Cdc42 and its regulation during cytokinesis is not well understood. Using biochemical and imaging approaches in budding yeast, we demonstrate that Cdc42 activation peaks during the G1/S transition and during anaphase but drops during mitotic exit and cytokinesis. Cdc5/Polo kinase is an important upstream cell cycle regulator that suppresses Cdc42 activity. Failure to down-regulate Cdc42 during mitotic exit impairs the normal localization of key cytokinesis regulators-Iqg1 and Inn1-at the division site, and results in an abnormal septum. The effects of Cdc42 hyperactivation are largely mediated by the Cdc42 effector p21-activated kinase Ste20. Inhibition of Cdc42 and related Rho guanosine triphosphatases may be a general feature of cytokinesis in eukaryotes.

/pdf/inhibition-of-cdc42-during-mitotic-exit-is-required-for-11vkuilnv5.pdf

Inhibition of Cdc42 during mitotic exit is required for cytokinesis

In many cells, morphogenetic events are coordinated with the cell cycle by cyclin-dependent kinases (CDKs). For example, many mammalian cells display extended morphologies during interphase but round up into more spherical shapes during mitosis (high CDK activity) and constrict a furrow during cytokinesis (low CDK activity). In the budding yeast Saccharomyces cerevisiae, bud formation reproducibly initiates near the G1/S transition and requires activation of CDKs at a point called “start” in G1. Previous work suggested that CDKs acted by controlling the ability of cells to polarize Cdc42, a conserved Rho-family GTPase that regulates cell polarity and the actin cytoskeleton in many systems. However, we report that yeast daughter cells can polarize Cdc42 before CDK activation at start. This polarization operates via a positive feedback loop mediated by the Cdc42 effector Ste20. We further identify a major and novel locus of CDK action downstream of Cdc42 polarization, affecting the ability of several other Cdc42 effectors to localize to the polarity site.

https://rupress.org/jcb/article-pdf/218/1/171/1381517/jcb_201806196.pdf

Koji Saito

Papers

Symmetry-Breaking Polarization Driven by a Cdc42p GEF-PAK Complex

Inhibition of Cdc42 during mitotic exit is required for cytokinesis

Cell-cycle control of cell polarity in yeast.

Response: GEF localization, not just activation, is needed for yeast polarity establishment