Bell, GP; (2014) The roles and regulation of the Drosophila Lgl tumour suppressor in cell division. Doctoral thesis , UCL (University College London).

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Abstract

Cell polarity is a fundamental feature of most cells, and is required for a diverse range of cell functions. A conserved set of proteins is involved in the establishment and maintenance of cell polarity. Several of these polarity proteins in Drosophila are recognized as neoplastic tumour suppressors, and loss of cell polarity in general has been linked to cancer malignancy. Although much is known about the general role of the polarity proteins, many questions still remain about the details and extent of their functions. I have focused on the Lgl protein in Drosophila epithelia: a basolaterally-localized tumour suppressor. In mitosis, Lgl undergoes a dramatic relocalisation away from the plasma membrane into the cytoplasm. I have found that this is regulated by direct phosphorylation by the Aurora cell cycle kinases: this is in contrast to the regulation of Lgl in interphase polarity, which is mediated by aPKC. The mitotic relocalisation event appears to play an important role in the correct orientation of the mitotic spindle and cell division in epithelia, which may be necessary for maintaining tissue integrity. Thus in addition to the established role for Lgl in cell polarity, my work suggests a novel function for Lgl during mitosis.

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