I hope (optimistically), with my collaborators, to develop a conceptual model of how macropinocytosis occurs in Dictyostelium amoebae.
Cells use macropinocytosis for the large-scale uptake of medium into micron-sized vesicles. There, it is digested by lysosomal enzymes and nutrients and other useful molecules extracted. Cancer cells and amoebae can feed this way and macropinocytosis underpins antigen uptake by immune cells, as well as providing a back door into cells for both drugs and viruses.
A key aspect of macropinocytosis is the ability of cells to project cups from the plasma membrane and then close them. Dictyostelium cells form domains of the signalling lipid PIP3 in the plasma membrane, around which macropinocytic cups form. We have proposed that these domains actually shape the cups by recruiting catalysts of actin polymerization to their periphery, as shown below with reporters for the Scar/WAVE complex (green) and PIP3 (red).
We are using lattice light sheet microscopy to map the components of macropinocytic cups and follow the dynamics of the PIP3 domains as cups expand and close, with the aim of producing a conceptual model of how this occurs. This work is in close collaboration with Till Bretschneider and Josiah Lutton (Warwick University) and Jason King (Sheffield University), as well as James Manton (LMB).
- Hoeller, O., Bolourani, P., Clark, J., Stephens, L.R., Hawkins, P.T., Weiner, O.D., Weeks, G. & Kay, R.R. (2013) Two distinct functions for PI3-kinases in macropinocytosis. J. Cell Sci. 126, 4296-4307.
- Bloomfield, G., Traynor, D., Sander, S.P., Veltman, D., Pachebat, J.A. & Kay, R.R. (2015). Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium. eLife 4: 10.7554/eLife; 4:04940.
- Bloomfield, G. & Kay, R.R. (2016). Uses and abuses of macropinocytosis. J. Cell Sci. 129, 2697-2705.
- Veltman, D.M., Williams, T.D., Bloomfield, G., Chen, B-C., Betzig, E., Insall, R.H. & Kay, R.R. (2016). A plasma membrane template for macropinocytic cups. eLife; 5:e20085; doi:10.7554/e20085.
- Williams, T.D. & Kay, R.R. (2018). The physiological regulation of macropinocytosis during Dictyostelium growth and development. J. Cell Sci. 131, jcs213736. doi:10.1242/jcs.213736.
- King, J.S. & Kay, R.R. (2019). The origins and evolution of macropinocytosis. Phil. Trans. R. Soc. B. 374: 20180158
- William, T.D., Sew-Yeu Peak-Chew, S-Y., Paschke, P. & Kay, R.R. (2019). Akt and SGK kinases are required for efficient feeding by macropinocytosis. J. Cell Sci. 132, jcs224998. doi:10.1242/jcs.224998
- Kay, R.R. (2021). Macropinocytosis: Biology and mechanisms. Cells & Development. https://doi.org/10.1016/j.cdev.2021.203713