Drosophila Neuronal Cell Biology

Research interests

We are interested in signaling processes that regulate neuronal function - both their basic biology, and their relevance to neurodegenerative disease. Of particular interest are the membrane traffic events relevant to these processes, using Drosophila as a model.

Membrane traffic and hereditary spastic paraplegia

We want to understand the cellular roles of proteins mutated in a class of motor neuron disease, hereditary spastic paraplegia (HSP). HSPs affect longer corticospinal motor tract axons, suggesting axon transport defects. However, most HSP genes encode intracellular membrane proteins, with no overt roles in axon transport. Recently we characterised one HSP protein as a regulator of BMP receptor traffic and signaling. We now want to understand how it works, and whether any of the other affected proteins have similar roles.

Synaptic membrane traffic

Our earlier work to dissect the mechanisms of synaptic vesicle release and endocytosis has led to results including tetanus toxin transgenic flies, a widely used tool for behavioural studies, and the finding that amphiphysin is important for T-tubule formation in muscles. Current work is focused on how membrane deformation induced by proteins like amphiphysin and endophilin is coupled to other events in the synapse.

Diseases of aggregate-prone proteins

Many neurodegenerative diseases are caused by aggregate-prone proteins like those containing polyglutamine. However, we do not fully understand the cellular responses to such proteins - a basic biological problem that is also relevant to effective therapies, which are currently lacking. A genome-wide screen here is identifying additional proteins that contribute to polyglutamine toxicity, and is starting to identify new players in relevant cellular processes such as autophagy and apoptosis.

3 key publications

1. Wang X, Shaw WR, Tsang HT, Reid E, O'Kane CJ (2007) Drosophila spichthyin inhibits BMP signaling and regulates synaptic growth and axonal microtubules. Nat Neurosci 10: 177-85
2. Koh TW, Korolchuk VI, Wairkar YP, Jiao W, Evergren E, Pan H, Zhou Y, Venken KJ, Shupliakov O, Robinson IM, O'Kane CJ*, Bellen HJ* (2007) Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development. J Cell Biol 178: 309-22 (* Joint senior authors)
3. Korolchuk VI, Schütz MM, Gómez-Llorente C, Rocha J, Lansu NR, Collins SM, Wairkar YP, Robinson IM, O'Kane CJ (2007) Drosophila Vps35 function is necessary for normal endocytic trafficking and actin cytoskeleton organisation. J Cell Sci 120: 4367-76

Page updated 21 January 2010