Invited review Endocytosis in different lifestyles of protozoan parasitism: role in nutrient uptake with special reference to Toxoplasma gondii Bruno Robibaro, Heinrich C. Hoppe 1 , Mei Yang, Isabelle Coppens, Hua ˆn M. Ngo ˆ, Timothy T. Stedman, Kerstin Paprotka, Keith A. Joiner * Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, LCI, 808333 Cedar Street, New Haven, CT 06520-8022, USA Received 26 January 2001; received in revised form 6 April 2001; accepted 6 April 2001 Abstract A fundamental property of any eukaryotic cell is endocytosis, that is the ability to take up external fluid, solutes and particulate matter into membrane-bound intracellular vesicles by various mechanisms. Toxoplasma gondii is an intracellular protozoan parasite of the phylum Apicomplexa with a wide geographical and host range distribution. Significant progress in studying the cell biology of this parasite has been accomplished over the last few years. Only recently endocytic compartments and endocytic trafficking have come to a closer dissection in T. gondii. In this review, we discuss the evidence for an endocytic compartment and present a model for an endocytic pathway in Toxoplasma against a background of endocytosis in kinetoplastida and the extensive insights gained from mammalian and yeast cells. q 2001 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved. Keywords: Endocytosis; Protozoa; Apicomplexa; Kinetoplastida; Rab proteins; Membrane trafficking; Nutrient acquisition 1. Introduction Endocytosis is a function common to all mammalian cells and serves many important cellular functions including the regulation of cell-surface receptor expression, maintenance of cell polarity, and antigen presentation (Mellman, 1996). The basic task accomplished by the process of endocytosis in mammalian cells is the uptake of extracellular fluid and macromolecules from the external environment and the maintenance of cellular homeostasis through the retrieval of proteins and lipids delivered to the plasma membrane by secretion (Mukherjee et al., 1997). Here we focus on the role or what is known about this basic cell biological function in four species of protozoa, the Apicomplexa Toxo- plasma gondii and Plasmodium spp., and the Kinetoplastida Leishmania spp. and Trypanosoma spp. Special emphasis in the course of this review is given to Toxoplasma. 2. Fluid-phase endocytosis and nutrient acquisition As an obligate intracellular pathogen that actively invades and resides in a wide variety of nucleated vertebrate cells, Toxoplasma has elaborated a battery of specialised secretory organelles (micronemes, rhoptries and dense gran- ules) that mediate host cell attachment and invasion, and the formation and maturation of the parasitophorous vacuole (PV) (Dubremetz et al., 1998; Ngo ˆ et al., 2000). In addition to these regulated exocytic events, the parasite contains an assemblage of antigens that are attached to the plasma membrane by a C-terminal glycosylphosphatidylinositol (GPI) (Boothroyd et al., 1998), including two putative receptors for immunoglobulin (Fc) (Vercammen et al., 1998) and fetuin (Gross et al., 1993). Surface antigens are presumably delivered to the plasma membrane by a consti- tutive secretory pathway (Karsten et al., 1998), which includes an extensive endoplasmic reticulum and a well developed Golgi stack (Hager et al., 1999). The invasive nature of Toxoplasma and its intracellular residence in a specialised compartment clearly necessitates extensive exocytosis activity, however only recently aspects of the physiological significance of endocytosis in the lifestyle of this parasite could be elucidated (Coppens et al., 2000; Robibaro et al., unpublished). International Journal for Parasitology 31 (2001) 1343–1353 0020-7519/01/$20.00 q 2001 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved. PII: S0020-7519(01)00252-1 www.parasitology-online.com * Corresponding author. Tel.: 11-203-785-4140; fax: 11-203-785-3864. E-mail address: keith.joiner@yale.edu (K.A. Joiner). 1 Present address: Department of Medical Microbiology, University of Cape Town Medical School, Observatory 7925, South Africa.