The roles and regulations of the neuronal cytoskeleton are complex. Simple genetic model organisms such as Drosophila can help to tackle this complexity. A nice example has just been published by Frederic Saudou and colleagues in Cell (Zala et al, 2013). They show that ATP produced by mitochondria is dispensable for fast axonal transport. Instead, GAPDH (glyceraldehyde 3-phosphate dehydrogenase) localises on transported vesicles and performs local glycolysis, thus providing ATP as “on-board energy” for the motor proteins. This is an exciting and fundamentally new concept that makes axonal transport over these enormous distances far better understandable. Importantly, fly genes encoding cytoskeletal machinery are well conserved with mammals, implying that Drosophila‘s proven track-record in solving complex biological problems and delivering evolutionary conserved mechanisms and concepts (Bellen et al., 2010) will hold true also in this case.
This notion is nicely illustrated by a beautiful recent study from Casper Hoogenraad and colleagues who demonstrated the fundamental roles of mammalian TRAK1 and 2 (TRAFFICKING PROTEIN, KINESIN-BINDING) in linking mitochondria to motor proteins during microtubule-based axonal and dendritic transport (van Spronsen et al., 2013). The TRAK homologue Milton and its essential roles in mitochondrial transport were first discovered in Drosophila (Stowers et al., 2002). As expected, matters turn now out to be more complex in mammals. However, the fundamental principles are shared, and this is where the fly can be used as a powerhouse for new ideas and discoveries, inspiring research on higher animals or even human disease.
- Zala, D., Hinckelmann, M.-V., Yu, H., Lyra da Cunha, Marcel M., Liot, G., Cordelières, Fabrice P., Marco, S., and Saudou, F. (2013). Vesicular glycolysis provides on-board energy for fast axonal transport. Cell 152, 479-491 –LINK
- Bellen, H. J., Tong, C., and Tsuda, H. (2010). 100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future. Nat Rev Neurosci 11, 514-522 – LINK
- van Spronsen, M., Mikhaylova, M., Lipka, J., Schlager, Max A., van den Heuvel, Dave J., Kuijpers, M., Wulf, Phebe S., Keijzer, N., Demmers, J., Kapitein, Lukas C., Jaarsma, D., Gerritsen, Hans C., Akhmanova, A., and Hoogenraad, Casper C. (2013). TRAK/Milton motor-adaptor proteins steer mitochondrial trafficking to axons and dendrites. Neuron 77, 485-502 –LINK
- Stowers, R. S., Megeath, L. J., Gorska-Andrzejak, J., Meinertzhagen, I. A., and Schwarz, T. L. (2002). Axonal transport of mitochondria to synapses depends on milton, a novel Drosophila protein. Neuron 36, 1063-1077 – LINK