Regulation of phagocytosis and endo-phagosomal trafficking pathways in Dictyostelium discoideum

Phagocytosis, a critically important process employed by leukocytes against invading pathogens, is an actin-dependent clathrinin-dependent process tha t results in the internalization of particles > 0.5 mum in diameter. Phagoc ytosis consists of a number of stages, including the binding of particles t o the cell surface via interaction with a receptor, engulfment of the parti cle by pseudopod extension, and fission and fusion reactions to form phago- lysosomes. Much remains to be learned concerning the molecular mechanisms t hat regulate particle internalization and phagosome maturation. Dictyosteli um is a genetically tractable professional phagocyte that has proven useful in determining the molecular steps involved in these processes. We will su mmarize, in this chapter, what we currently understand concerning the molec ular mechanisms that regulate the process of phagocytosis in Dictyostelium, and we will compare and contrast this body of information with that availa ble describing phagocytosis in higher organisms. We will also present curre nt information that suggests that macropinocytosis, a process morphological ly similar to phagocytosis, utilizes a different signaling pathway than pha gocytosis. Finally, we will discuss the process of maturation of phagosomes , which requires membrane trafficking events, and we will summarize data th at support the use of Dictyostelium as a model to determine how intracellul ar pathogens survive. (C) 2001 Published by Elsevier Science B.V.