rest The author is named as an inventor on patents relating to the use of CRTH2 antagonists in allergic and other diseases. `Professional’ phagocytes, including macrophages and Dictyostelium, a free-living, soil amoebae, have an ability to rapidly and efficiently internalize a variety of organisms or particles, a function that is vital for host defenses toward foreign invasion, tissue remodeling, and nutrient uptake. Macrophages, myeloid dendritic cells, and neutrophils can phagocytose microbial pathogens, which potentiates innate and adaptive immunity. The elimination Corresponding author. Laboratory of Cellular and Developmental Biology, National Institutes of Health, NIDDK, MMDS, Building 6/B1-22, NIH, Bethesda, MD 20892-2715, USA. Tel.: 1 301 496 3016; Fax: 1 301 496 5239; E-mail: [email protected] 1 Present address: Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, MD, USA Received: 20 January 2005; accepted: 24 May 2005; published online: 16 June 2005 of apoptotic cells by phagocytes is also essential to control immune and inflammatory response, as well as to regulate tissue homeostasis during development and to prevent necrosis. In Dictyostelium, phagocytosis of bacteria and fungi is essential for nutrient capture in the wild. The AEB 071 phagocytic process begins with particle recognition and cell surface binding. As the plasma membrane and cortical cytoskeleton become reorganized, a phagocytic cup is formed. The particle is then engulfed and internalized, forming the early phagosome, a unique organelle that is trafficked through a series of early and late endocytic membrane compartments that define the phago-lysosomal pathway. Ultimately, an ingested microbe is destroyed. Phagosome biogenesis has recently been subject to superb proteomic approaches. While, many new and unexpected components have been described that provide unique perspective, mechanistic linkages remain to be fully explored. Furthermore, although protection from microbial invasion is a primary immunity response, little is known about recognition specificity or the molecular mechanisms that regulate phagocytic uptake and phagosome trafficking. In addition, the infectious nature of Mycobacterium, Salmonella, Legionella, and other pathogenic parasites, which are readily susceptible to cellular uptake but PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19803812 are able to subvert intracellular destruction and to propagate productively within phagocytes, is only partially understood at the host level. The professional phagocyte Dictyostelium is a genetically and biochemically tractable organism for defining molecular mechanisms that regulate phagocytosis. Biochemical and genetic analyses indicate that Dictyostelium and mammalian macrophages/neutrophils have strong similarities in endocytosis, despite their separation by more than 500 000 000 years. The shared role of Rac1 during the phagocytosis of yeast in Dictyostelium and of apoptotic cells in Caenorhabditis elegans and mammalian systems underscores this relationship. In addition, Dictyostelium exhibit phagocytic rates that are several-fold in excess of those in macrophages and neutrophils and, like macrophages, Dictyostelium cells are subject to pathogenic infection by Mycobacterium and Legionella. We have identified two novel LIM domain proteins, LimF and ChLim, from Dictyostelium that are 
binding partners and that coordinate with activated, GTP-bound Rab21 to regulate phagocytosis. The in vivo functions of LimF, ChLim, and Rab21 in Dictyosteli