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Cytoskeleton polarisation in Drosophila

Khanal, I; (2016) Cytoskeleton polarisation in Drosophila. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Epithelial cells are polarised into distinct domains by the core apical and basolateral determinants. Cell polarity is critical for tissue integrity and also plays an important role in many morphogenetic processes. How polarity determinants act to polarise the cytoskeleton and orient cellular functions is unclear. The work presented in this thesis examines how the different components of the cytoskeleton – the actin filaments, Spectrins and microtubules – become polarised in response to polarity determinants and how this polarisation contributes to different cellular behaviours in development. Our results identify a novel role for Hippo signalling in linking cell polarity determinants to polarisation of the actin cytoskeleton during Drosophila border cell migration. We find that Hippo signalling acts independently of canonical Yorkie nuclear signalling. Instead, Warts phosphorylates and inhibits the actin regulator Enabled to activate F-actin Capping protein activity, thus polarising the actin cytoskeleton by restricting F-actin polymerisation to the outer rim of the migrating cluster. In addition to Hippo’s link with F-actin, our work also demonstrates a link between Hippo and the Spectrin cytoskeleton. We show that apical and basolateral Spectrins are upstream regulators of Hippo signalling and act as potential mechanosensors to regulate growth. Finally, we also show that polarity determinants are important for polarising microtubules in Drosophila follicle cells. We demonstrate that the Spectrin-associated proteins Patronin and Shortstop are required to polarise microtubules along the apical-basal axis of epithelial cells. These microtubules direct apical transport of Rab11-positive vesicles containing the microvilli determinant Cadherin99C via the Dynein motor and its adaptor protein Nuf. At the apical cortex, Rab11-positive vesicles switch to actin-based transport via the MyosinV motor and its adaptor protein dRip11 to direct apical delivery of Cadherin99C to drive biogenesis of apical microvilli. Taken together, our work demonstrates how determinants of apical-basal polarity can control polarisation of the cytoskeleton to direct diverse cellular processes.

Type: Thesis (Doctoral)
Title: Cytoskeleton polarisation in Drosophila
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1474496
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