Oxidative stress induced regulation of synaptic growth in the nervouse system

We have identified a role for oxidative stress (OS) in the regulation of synapse growth. Drosophila larvae exposed to an burden have overgrown neuromuscular synapses. This overgrowth is mediated by the Jun-kinase cascade and the AP-1 transcription factor. We have observed that when the OS burden is cytoplasmic, the AP-1 dimer is composed of Fos homodimers. When the OS burden is mitochondrial in origin, the AP-1 dimer is composed of Fos and Jun heterodimers. Function of autophagy genes is also required for synapse overgrowth. We have more recently identified a role for the Parkinson's Disease related protein DJ-1 in mediating synaptic growth under conditions of oxidative stress and implicate the PTEN signalling cascade in mediating DJ-1 responses in synapse growth.

Two very high profile research papers result from this work:

Lu, Y., Zhang, Z., Sun, D., Sweeney, S.T. and Gao, F.B. (2013) Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is required for autophagosome maturation. Molecular Cell, 52 (2): 264-271

Milton, V.J., Jarrett, H.E., Gowers, K., Briggs, L., Chalak, S., Robinson, I.M. and Sweeney, S.T. (2011) Oxidative stress induces overgrowth of the Drosophila neuromuscular junction. P.N.A.S. 108:17521-26.