The Involvement of Adaptor Protein Complexes in Phagocytosis

Candidate: Muhammad Butt
Supervisor: Dr. Roberto Botelho

ABSTRACT

Phagocytosis is an essential process involved in innate immunity. It is a multi-stage process starting with phagocytic uptake, followed by phagosome maturation, and finally phagosome resolution. The first two stages of phagocytosis have been studied thoroughly over the past decades but very little is known about the terminal phagosome resolution stage. The discovery of clathrin involvement in phagosome resolution has raised new speculations of the involvement of other membrane fission proteins such as the Adaptor Protein (AP) complexes some of which recruit clathrin to drive fission events inside the cell. Therefore, we aimed to study the involvement of AP-1, AP-2, and AP-3 in phagosome resolution, However, to account for downstream effects on phagosome resolution due to altered phagocytic uptake and phagosome maturation, we conducted research to explore the effects of silencing AP-1, AP-2, and AP-3 at each of the three main stages of phagocytosis. Our data reveal a role for AP-2 and AP-3 in phagocytic uptake, a role for AP-1 in phagosome maturation, and a novel role for AP-2 and AP-3 in phagosome resolution in a clathrin-dependent and clathrin-independent manner, respectively. Our observations will have a significant impact on future work concerning the molecular machinery involved in phagosome resolution as well as subsequent investigations studying the involvement of AP complexes in phagocytic uptake and phagosome maturation.