Malaria protease takes an indirect route

Awakening heterochromatin ites in the human genome once thought to be inert structural material are brought to life in response to stress, according to results from Jolly et al. (page 25). These inactive DNA stretches are binding sites for HSF1, a transcription factor that activates individual heat shock genes and accumulates in nuclear granules after heat shock. These granules were, like HSF1, expected to activate heat shock genes. So their recent localization to hetero-chromatic satellite III regions, which do not contain the major heat shock genes, was surprising. Jolly now shows that the stress granules activate transcription even in these repeat sequences. S Stress granules containing HSF1 (red) produce satellite III transcripts (green). Malaria protease takes an indirect route he bug that causes malaria feeds by gobbling up chunks of hemoglobin from the red blood cells it resides in. On page 47, Klemba et al. show how the parasite brings together this food source with its own enzymes that will degrade it. The results offer insight into how to treat this deadly disease. The parasite breaks down hemoglobin for nutrients in its specialized organelle called the food vacuole, using proteases such as plasmepsin II (PM II). Hemoglobin gets to the food vacuole in vesicles that pinch off from cytostomes—openings through the parasite plasma membrane that lead to the blood cell cytoplasm. But how the endogenous protease reaches the food vacuole to meet its substrate had not been defined, leading some researchers to wonder whether a direct targeting pathway exists from the ER to the food vacuole. The new results suggest this is not the case. Instead, the group sees that an inactive precursor form of the protease hitches a ride with hemoglobin in cytostome-derived vesicles. GFP fusions of the PM II precursor were seen to be secreted from the ER to cytostomes. From there, the fusions traveled in vesicles shared by hemoglobin to the food vacuole, where the precursor was processed to its active form. It is not clear whether PM II is sent directly to cytostomes or simply diffuses laterally once at the plasma membrane. If the former is true, a cytostome-targeted trafficking pathway might be a pathogen-specific target for drug treatments. ᭿ T PM II (labeled) is brought to the food vacuole (fv) in cytostomal vacuoles (cv). R chaperones need calcium to help them in their folding duties. Work on page 35 by Li and Camacho shows that …