@article {46423,
	title = {A contiguous compartment functions as endoplasmic reticulum and endosome/lysosome in Giardia lamblia.},
	journal = {Eukaryotic Cell},
	volume = {8},
	year = {2009},
	month = {2009 Nov},
	pages = {1665-76},
	abstract = {<p>The dynamic evolution of organelle compartmentalization in eukaryotes and how strictly compartmentalization is maintained are matters of ongoing debate. While the endoplasmic reticulum (ER) is classically envisioned as the site of protein cotranslational translocation, it has recently been proposed to have pluripotent functions. Using transfected reporter constructs, organelle-specific markers, and functional enzyme assays, we now show that in an early-diverging protozoan, Giardia lamblia, endocytosis and subsequent degradation of exogenous proteins occur in the ER or in an adjacent and communicating compartment. The Giardia endomembrane system is simple compared to those of typical eukaryotes. It lacks peroxisomes, a classical Golgi apparatus, and canonical lysosomes. Giardia orthologues of mammalian lysosomal proteases function within an ER-like tubulovesicular compartment, which itself can dynamically communicate with clathrin-containing vacuoles at the periphery of the cell to receive endocytosed proteins. These primitive characteristics support Giardia{\textquoteright}s proposed early branching and could serve as a model to study the compartmentalization of endocytic and lysosomal functions into organelles distinct from the ER. This system also may have functional similarity to the retrograde transport of toxins and major histocompatibility complex class I function in the ER of mammals.</p>
},
	keywords = {Endoplasmic Reticulum, Endosomes, Giardia lamblia, Lysosomes, Protozoan Proteins},
	issn = {1535-9786},
	doi = {10.1128/EC.00123-09},
	author = {Abodeely, Marla and DuBois, Kelly N and Hehl, Adrian and Stefanic, Sasa and Sajid, Mohammed and DeSouza, Wanderley and Attias, Marcia and Engel, Juan C and Hsieh, Ivy and Fetter, Richard D and McKerrow, James H}
}
@article {46420,
	title = {A parasite cysteine protease is key to host protein degradation and iron acquisition.},
	journal = {Journal of Biological Chemistry},
	volume = {283},
	year = {2008},
	month = {2008 Oct 24},
	pages = {28934-43},
	abstract = {<p>Cysteine proteases of the Clan CA (papain) family are the predominant protease group in primitive invertebrates. Cysteine protease inhibitors arrest infection by the protozoan parasite, Trypanosoma brucei. RNA interference studies implicated a cathepsin B-like protease, tbcatB, as a key inhibitor target. Utilizing parasites in which one of the two alleles of tbcatb has been deleted, the key role of this protease in degradation of endocytosed host proteins is delineated. TbcatB deficiency results in a decreased growth rate and dysmorphism of the flagellar pocket and the subjacent endocytic compartment. Western blot and microscopic analysis indicate that deficiency in tbcatB results in accumulation of both host and parasite proteins, including the lysosomal marker p67. A critical function for parasitism is the degradation of host transferrin, which is necessary for iron acquisition. Substrate specificity analysis of recombinant tbcatB revealed the optimal peptide cleavage sequences for the enzyme and these were confirmed experimentally using FRET-based substrates. Degradation of transferrin was validated by SDS-PAGE and the specific cleavage sites identified by N-terminal sequencing. Because even a modest deficiency in tbcatB is lethal for the parasite, tbcatB is a logical target for the development of new anti-trypanosomal chemotherapy.</p>
},
	keywords = {Animals, Animals, Genetically Modified, Catalytic Domain, Cysteine, Cysteine Endopeptidases, Endocytosis, Fluorescence Resonance Energy Transfer, Iron, Lysosomes, Microscopy, Electron, Transmission, Models, Biological, Protein Structure, Tertiary, RNA Interference, Transferrin, Trypanosoma brucei brucei},
	issn = {0021-9258},
	doi = {10.1074/jbc.M805824200},
	author = {O{\textquoteright}Brien, Theresa C and Mackey, Zachary B and Fetter, Richard D and Choe, Youngchool and O{\textquoteright}Donoghue, Anthony J and Zhou, Min and Craik, Charles S and Caffrey, Conor R and McKerrow, James H}
}
