Poster Presentation 2019 Hunter Cell Biology Meeting

Trafficking and Signalling from Macropinosomes in Microglia (#128)

Yu Hung 1 , Jennifer L Stow 1 , Adam Wall 1
  1. Institute for Molecular Bioscience, Centre for Inflammation and Disease Research, University of Queensland, Brisbane, Australia

Macropinosomes are important cellular compartments that allow for the uptake of pathogens, nutrients and cellular debris but also function as key sites of signalling. Many trafficking proteins, including GTPases, are involved in macropinocytosis and also in receptor signalling on these membranes.  Our group has previously identified Rab8a and its effector, PI3Kg as regulators of Akt/mTOR signalling downstream of Toll-like receptors (TLRs) in macrophages. Most recently we have identified low dentistry lipoprotein receptor-like protein 1 (LRP1) as a cross talk receptor that recruits Rab8a/PI3Kg in response to activation of TLRs. The LRP1/Rab8a complex, which acts on signalling at the level of macropinosomes, is an important regulator of TLR-induced inflammation. LRP1 has other roles in modulating inflammation and it is heavily implicated in Alzheimer’s disease pathogenesis. The role of LRP1 recruited Rab8a/PI3Kg however is poorly characterised in microglia, innate immune cells of the central nervous system tasked with cytokine production of clearance of cellular debris. Here we aim to elucidate where Rab8a and LRP1 intersect on signalling membranes during internalisation from the cell surface and their recycling trajectories in these cells. We have defined the trajectories and machinery involved in Rab8a and LRP1 trafficking from macropinosomes in live microglial cells. These results will allow us to better understand trafficking and activation of LRP1 as a modulator of inflammation and as a clearance receptor in microglia and reveal how the Rab8a/PI3Kg complex is recruited and trafficked for TLR signalling and inflammation.