Identifying targets of the MAST kinase Drop out through genetic and proteomic analysis in Drosophila melanogaster

The drop out (dop) gene is the single homolog of the mammalian MAST (microtubule-associated serine/threonine) kinase family in Drosophila melanogaster. The MAST kinases are a poorly understood family of proteins which have been implicated in human diseases, such as neurodegeneration and breast cancer. Previous work revealed that dop mutation affects the process of cellularisation, the process by which cells are first formed after 13 cycles of syncytial divisions. Cellularisation produces a polarised epithelial monolayer around the periphery of embryos. Analysis of cellularisation in dop mutants revealed defects in the establishment of epithelial polarity. Defects in dop mutants are used as a model to further understand MAST kinase function. In this work, a panel of dop mutants is characterised molecularly and phenotypically, revealing that the kinase domain of Dop is the most important for its function. Therefore, an important aspect in understanding of Dop function is to identify its substrates. Potential substrates of Dop are identified by a SILAC and phosphoproteomic approach of Drosophila embryos. Substrates identified from this approach may help in understanding the function of Dop during development. In conjunction with the proteomic approach, interactors of dop are also identified through genetic methods. Defects during and after cellularisation indicate a role for Dop in the regulation of Dynein-mediated microtubule transport. In this work, the function of Dop in microtubule transport is examined through genetic interactions between dop mutants and mutants of the Dynein and Dynactin complexes. Furthermore, Dop is identified as a regulator of the Hedgehog signalling pathway, and is required in signal transduction.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

University of Dundee

Year dc:date.issued

2013

Author dc:creator

• Langlands, Alistair

Advisor dc:contributor.advisor

• Muller, Hans-Arno

Language dc:language

eng

Identifier

oai:discovery.dundee.ac.uk:studenttheses/f19f1d07-de7f-4939-9fb1-03754e2e764e

OAI identifier oai:identifier

oai:discovery.dundee.ac.uk:studenttheses/f19f1d07-de7f-4939-9fb1-03754e2e764e