Spatiotemporal mechanisms for actomyosin ring assembly and contraction in budding yeast cell division

Dissertation presented to obtain the Ph.D degree in Molecular Medicine

Animal and yeast cells use a contractile ring that is attached to the plasma membrane to create a cleavage furrow that partitions a cell into two in the latest step of cell division. The contractile ring is a network of actin and myosin-II motor filaments embedded in a complex and compact protein core structure at the cell division site. In the absence of myosin-II, cells fail to assemble the contractile ring pursuing death or rapidly evolving divergent pathways to restore growth and cytokinesis, an event associated to aneuploidy, a common trait in cancer development and progression. The molecular mechanisms underlying myosin-II localization and function at the cell division site with actin ring assembly and contraction remain poorly understood. Based on analogy to the striated muscle, it has been classically proposed that contractile stress in the actomyosin ring is generated via a “sliding filament” mechanism in which bipolar myosin-II motor filaments walk along actin filaments, within organized sarcomere-like arrays. However, ultra-structural and genetic studies in different cellular systems have shown that contractile rings are more complex than striated muscles, and in some examples the motor activity can actually be dispensable for the contractibility of the cytokinetic ring.(...)

PhD fellowship awarded by the Rong Li laboratory and a previous awarded fellow of the GABBA PhD program at the Faculty of Medicine, University of Porto, Portugal and the Portuguese Foundation for Science and Technology, Portugal. Apoio financeiro da Fundação para a Ciência e Tecnologia e do Fundo Social Europeu no âmbito do Quadro Comunitário de Apoio, BD n°SFRH/BD/11760/2003.