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Title: Dissecting Polo kinase recruitment to the centrosome
Author: Alvarez Rodrigo, Ines
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2020
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Polo kinase is a major regulator of the cell cycle. Polo is present at many different subcellular structures, including centrosomes. Centrosomes are formed when mother centrioles recruit pericentriolar material (PCM) around themselves. The PCM expands dramatically in preparation for mitosis, in a process that relies on Polo phosphorylation of the PCM protein Cnn. Polo is also known to regulate centriole disengagement, and Polo binding to the centriolar protein Sas-4 is crucial for Asl recruitment to daughter centrioles during their conversion into fully functional mothers. The primary aim of my thesis was to fully characterise how Polo is recruited to centrosomes to perform its different functions. As a model, I use syncytial fly embryos. In addition to the previously known Polo binding site in Sas-4, I found that the PCM protein Spd-2 directly interacts with the PBD domain of Polo. While Spd-2 is not required for Polo recruitment to the centriole, it is crucial to recruit Polo to the PCM. I propose that this interaction is part of a Spd-2/Polo/Cnn positive feedback loop that drives mitotic PCM assembly. Furthermore, I found that a third protein (Ana1) is required for overall Polo recruitment to the centrosome. Ana1 has been previously linked to Asl recruitment and/or maintenance and centriole conversion. Losing Ana1-mediated Polo recruitment did not affect these processes, but it did severely hinder mitotic PCM expansion. I propose that, independently of its Asl-related role, Ana1 acts as a crucial reservoir of centriolar Polo. Thus, centriolar Polo recruited via Ana1 can phosphorylate Spd-2 to allow it to bind the PBD, in an example of Polo “self-priming”.
Supervisor: Raff, Jordan Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available