GROWTH AND DIVISION

Coordination of cell growth and cell division

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 Obiettivo del progetto (Objective)

'The dynamic properties of the cytoskeleton facilitate cell growth and cell division. The pattern and amount of cell growth, combined with the timing of cell division, generates the spectrum of cell sizes and shapes found in nature. Despite the fundamental importance of these processes, remarkably little is known about how cell growth and cell division are coordinated. In budding yeast, a core component of the cell cycle machinery, cyclin dependent kinase 1 (Cdk1), triggers polarization of the actin cytoskeleton and growth of a new cell early in the cell cycle. This places Cdk1 activity at the hub between the control of polarized cell growth and cell division. My work has demonstrated that signaling from Cdk1 activates highly conserved Rho family GTPases, including Cdc42, which both establish and maintain an axis of polarity along which cell division occurs. Cdk1 triggers the activation of Cdc42 via phosphorylation of a novel multi-protein complex that I have identified by mass spectrometry, comprising of multiple Cdc42 regulators. Exploring the mechanisms by which Cdc42 is activated by Cdk1 activity, and the targets that lie downstream of Cdc42, will therefore improve our understanding of how cell growth and cell division are coordinated, a key unresolved issue in cell biology.'

Introduzione (Teaser)

Cell growth and division are fundamental properties for the existence of life. The molecular mechanisms that govern the coordination between these two processes remain unresolved.

Descrizione progetto (Article)

Collectively, the steps implicated for growth and division are known as the cell cycle, normally a tightly controlled process. The discovery of the cell cycle revolutionised the field of biology and helped us understand how life is sustained. The cell cycle pattern contributes to the final size and shape of cells and aberrant cell division leads to cancer.

The key objective of the EU-funded 'Coordination of cell growth and cell division' (GROWTH AND DIVISION) project was to investigate the mechanisms that coordinate cell growth with progression through the cell cycle. As the regulatory mechanisms responsible for cell cycle progression are remarkably conserved among eukaryotes, researchers used the budding yeast Saccharomyces cerevisiae as a model system.

Their efforts concentrated on the role of the core cell cycle component cyclin dependent kinase 1 (Cdk1) which triggers polarised growth in yeast. They generated yeast mutants. Using advanced microscopy methods they found that Cdk1 played a significant role in regulating membrane trafficking to coordinate membrane growth with cell cycle progression.

Investigation of the underlying mechanism indicated that Cdk1 worked through Cdc42 to reorganise the endocytic and exocytic membrane trafficking vesicles. Using specialised photo conversion methodology, scientists succeeded in tracking and quantitating the dynamics of exocytic vesicles in over 400 yeast mutants. This helped them identify additional critical components that contribute to membrane vesicle trafficking.

The findings of the GROWTH AND DIVISION study provide a novel link between the cell cycle and cell growth. This previously undocumented role of Cdk1 in membrane trafficking could form the basis for future studies towards resolving the enigma of cell growth regulation.