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Acidocalcisomes of Trypanosoma brucei have an inositol 1,4,5-trisphosphate receptor that is required for growth and infectivity
Guozhong Huang, Paula J. Bartlett, Andrew P. Thomas, Silvia N. J. Moreno and Roberto Docampo
Proceedings of the National Academy of Sciences of the United States of America
Vol. 110, No. 5 (January 29, 2013), pp. 1887-1892
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/41992135
Page Count: 6
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Acidocalcisomes are acidic calcium stores rich in polyphosphate and found in a diverse range of organisms. The mechanism of Ca²⁺ release from these organelles was unknown. Here we present evidence that Trypanosoma brucei acidocalcisomes possess an inositol 1,4,5-trisphosphate receptor (TblP₃R) for Ca²⁺ release. Localization studies in cell lines expressing TblP₃R in its endogenous locus fused to an epitope tag revealed its partial colocalization with the vacuolar proton pyrophosphatase, a marker of acidocalcisomes. IP₃ was able to stimulate Ca²⁺ release from a chicken B-lymphocyte cell line in which the genes for all three vertebrate IP₃Rs have been stably ablated (DT40-3KO) and that were stably expressing TblP₃R, providing evidence of its function. IP₃ was also able to release Ca²⁺ from permeabilized trypanosomes or isolated acidocalcisomes and photolytic release of IP₃ in intact trypanosomes loaded with Fluo-4 elicited a transient Ca²⁺ increase in their cytosol. Ablation of TblP₃R by RNA interference caused a significant reduction of IP₃-mediated Ca²⁺ release in trypanosomes and resulted in defects in growth in culture and infectivity in mice. Taken together, the data provide evidence of the presence of a functional IP₃R as a Ca²⁺ release channel in acidocalcisomes of trypanosomes and suggest that a Ca²⁺ signaling pathway that involves acidocalcisomes is required for growth and establishment of infection.
Proceedings of the National Academy of Sciences of the United States of America © 2013 National Academy of Sciences