Many developmentally regulated membrane proteins of lymphocytes are ecto-enzymes, with their active sites on the external surface of the cell. These enzymes commonly have peptidase, phosphodiesterase or nucleotidase activity. Their biological roles are just beginning to be discovered. Although their expression is usually associated with particular stages of lymphoid differentiation, the same gene products are often expressed on the surface of certain non-lymphoid cell types outside the immune system, indicating that their functions cannot be unique to lymphocytes, nor can they be ubiquitous. The plasma cell membrane protein PC-1 (phosphodiesterase I; EC 3.1.4.1/nucleotide pyrophosphatase; EC 3.6.1.9), which was one of the first serological markers for lymphocyte subsets to be discovered, is a typical example. Within the immune system, PC-1 is confined to plasma cells, which represent about 0.1% of lymphocytes. However, PC-1 is also expressed on cells of the distal convoluted tubule of the kidney, chondrocytes, osteoblasts, epididymis and hepatocytes. Recent work has shown that PC-1 is a member of a multigene family of ecto-phosphodiesterases that currently has two other members, PD-1 alpha (autotaxin) and PD-1 beta (B10). Within this family, the extracellular domains are highly conserved, especially around the active site. In contrast, the transmembrane and cytoplasmic domains are highly divergent. Individual members of the eco-phosphodiesterase family have distinct patterns of distribution in different cell types, and even within the same cell. For example, PC-1 is present only on the basolateral surface of hepatocytes, while B10 (PD-1 beta) is confined to the apical surface. Analysis of conservation and differences in the sequence of their cytoplasmic tails may illuminate intracellular targetting signals. Ecto-phosphodiesterases may play a part in diverse activities in different tissues, including recycling of nucleotides. They may also regulate the concentration of pharmacologically active extracellular compounds such as adenosine or its derivatives and cell motility. Some members may modulate local concentrations of pyrophosphate, and hence influence calcification in bone and cartilage.

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The oocyst wall of apicomplexan parasites protects them from the harsh external environment, preserving their survival prior to transmission to the next host. If oocyst wall formation could be disrupted, then logically, the cycle of disease transmission could be stopped, and strategies to control infection by several organisms of medical and veterinary importance such as Eimeria, Plasmodium, Toxoplasma, Cyclospora, and Neospora could be developed. Here, we show that two tyrosine-rich precursor glycoproteins, gam56 and gam82, found in specialized organelles (wall-forming bodies) in the sexual stage (macrogamete) of Eimeria maxima are proteolytically processed into smaller glycoproteins, which are then incorporated into the developing oocyst wall. The identification of high concentrations of dityrosine and 3,4-dihydroxyphenylalanine (DOPA) in oocyst extracts by high-pressure liquid chromatography, together with the detection of a UV autofluorescence in intact oocysts, implicates dityrosine-and possibly DOPA-protein cross-links in oocyst wall hardening. In addition, the identification of peroxidase activity in the wall-forming bodies of macrogametes supports the hypothesis that dityrosine-and DOPA-mediated cross-linking might be an enzyme-catalyzed event. As such, the mechanism of oocyst wall formation in Eimeria, is analogous to the underlying mechanisms involved in the stabilization of extracellular matrices in a number of organisms, widely distributed in nature, including insect resilin, nematode cuticles, yeast cell walls, mussel byssal threads, and sea urchin fertilization membranes.Eimeria maxima is an intestinal parasite of chickens and is one of the causative agents of coccidiosis, contributing to costs on the order of billions of dollars per year to the poultry meat industry (34, 37). The life cycle of Eimeria includes asexual and sexual stages of development that lead to the formation of the infective form of the parasite, the oocyst (23). Prior to excretion, the oocyst is encapsulated by a hard barrier, the oocyst wall, which protects the parasite from the harsh external environment. Once excreted from the host, the oocyst develops further (sporulation) and is passed onto the next host via the fecal-oral route.The oocyst wall is a structure that is vital to the parasite and ensures the organism's survival and transmission to the next host. It is bilayered, composed of a 10-nm-thick lipid outer layer and a 90-nm-thick glycoprotein inner layer arising from the contents of specialized organelles called wall-forming bodies, which are found exclusively in the sexual stage (macrogamete or macrogametocyte) of the parasite (13,26,31). Progress towards understanding the mechanism of oocyst wall formation in Eimeria has been difficult due to the lack of a good culture system for studying the sexual stages of Eimeria and problems associated with isolating large quantities of parasites. However, with the advent of new technologies in proteomics and molecular biology, together with improved methods for the increased ...