Regulation of fission yeast cell polarity by stress-response pathways
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Date
07/07/2017Item status
Restricted AccessEmbargo end date
31/12/2100Author
Mutavchiev, Delyan Rumenov
Metadata
Abstract
Cell polarisation is a key biological process crucial for the functioning of
essentially all cells. Regulation of cell polarity is achieved through various processes
determined by both internal and external factors. An example of the latter is that cell
polarity can be disrupted or lost as a consequence of a variety of external stresses.
When facing such stresses, cells adapt to unfavourable conditions by activating a
range of molecular signalling pathways, collectively termed ‘stress response’. Despite
the connections between external stress and cell polarity, whether stress-response
signalling regulates cell polarisation and what the molecular basis for such regulation
remains an open question. The fission yeast Schizosaccharomyces pombe presents
an excellent biological platform to study the complexity of cell polarity regulation on a
systematic level. This study is aimed at understanding the functional relationship
between stress-response signalling and maintenance of cell polarity in this model
organism.
The findings presented in this thesis set the basis for establishing a functional
link between the activation of the S.pombe stress-response pathway and the activity
of the master regulator of cell polarity- the Rho GTPase Cdc42. Here, I describe
experiments that identify an active involvement of the stress-response mitogen-activated
kinase (MAPK) Sty1 in the dispersal of active Cdc42 from the sites of
growth. This new role for Sty1 occurs independently from its involvement in
transcription regulation and other previously identified signalling pathways involving
Sty1. Furthermore, I also find that Sty1’s involvement in Cdc42 regulation has direct
implications for fission yeast physiology as it is essential for the maintenance of
cellular quiescence upon nitrogen starvation. This thesis also focuses on identifying
the targets of Sty1 orchestrating the active Cdc42 disruption. Here, I describe a
candidate-based approach, where I investigate the role of proteins from the Cdc42
regulatory network during Sty1 activation. Additionally, I present a global phospho-proteomics
approach to identify novel targets of Sty1 and offer preliminary findings
which might explain Sty1’s involvement in Cdc42 regulation.