mRNA Localisation in Drosophila
Co-workers: Graeme Ball, Sam Cooper, James Halstead, Russell Hamilton, Suzanne McDermott, Carine Meignin, Richard Parton, Jan Soetaert, Ana Maria Valles, Tim Weil
A key question in biology is how different molecules are sorted and kept at their correct destinations within cells. For example, how mRNA localization and translational regulation target proteins to their site of function and facilitate memory and learning in the nervous system.
Considerable intracellular sorting is achieved by molecular motors transporting cargo along the cytoskeleton, a system analogous to a trains transporting cargo on train tracks. We have been studying the tickets (RNA signals) that determine which train (dynein motor) will be used by different passengers (RNA cargo) and how the ticket inspector (trans acting protein factors) chose which trains the passengers can travel on.
We have shown that the passengers are kept at the final destination by remaining attached to the engine (dynein motor) on the track (microtubules). Once it arrives at the destination, the cargo remains there even if the engine is switched off (ATPase activity of the motor is inhibited) and the driver and guard go home (motor cofactors inhibited).
We have been studying these processes in living cells using highly sensitive microscopy techniques, which can reveal the detailed dynamics of RNA movement. We are studying these processes in embryos and oocytes and in the nervous system.
- Parton, R., Hamilton, R., Ball, G., Yang, L., Cullen, F., Liu, W., Ohkura, H., and Davis, I. (2011). A Par-1 dependent graded bias in microtubule orientation establishes cell polarity in the Drosophila oocyte. Journal of Cell Biology, 194: 121-135
- Brown, A., Oddos, S., Dobbie, I., Alakoskela, J., Parton, R., Eissmann, P., Neil, P., Dunsby, C., French, P., Davis, I. and Davis, D. (2011) Remodelling of Cortical Actin where Lytic Granules dock at Natural Killer Cell Immune Synapses Revealed by Super-Resolution Microscopy. Plos Biol 7: e1000159
- McDermott SM, Meignin C, Rappsilber J, Davis I., Drosophila Syncrip binds the gurken mRNA localisation signal and regulates localised transcripts during axis specification., (2012) Biol Open. 1:488-97
- Zhang F, Wang J, Xu J, Zhang Z, Koppetsch BS, Schultz N, Vreven T, Meignin C, Davis I, Zamore PD, Weng Z, Theurkauf WE. (2012) UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery. Cell 151: 871-84
- Weil TT, Parton RM, Herpers B, Soetaert J, Veenendaal T, Xanthakis D, Dobbie IM, Halstead JM, Hayashi R, Rabouille C, Davis I. Drosophila patterning is established by differential association of mRNAs with P bodies. Nat Cell Biol. 2012 Dec;14(12):1305-13
Figure 1: Intracellular mRNA transport illustrated with a train analogy. The train tracks represent the polarized microtubule cytoskeleton, engines represent molecular motors (dynein and kinesin) and the passengers represent different RNA cargo (gurken, wingless ftz and oskar mRNA)
Figure 2: The movement of gurken (TGFalpha) RNA from the nurse cells into the oocyte in Drosophila egg chambers. After injection into the nurse cells, gurken RNA (red), assembles into particles that move through the ring canals (green), connecting the nurse cells (left) to the oocyte (right). The particles are shown as trails by superimposing multiple time points from a time lapse movie onto a single image
Figure 3: Syncytial blastoderm embryo expressing a nuclear GFP (green) injected with red RNA, which was allowed to fully localized followed by far red RNA (shown in cyan), which has not yet localized. Injection of inhibitory reagents can then assay distinct requirements for transport (blue RNA) and anchoring (red RNA) in the same living embryo
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