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Eminent Scholar, Department of Cellular Biology
350 B Paul D. Coverdell Center,
500 D.W. Brooks Drive
Athens, GA 30602
Phone: 706-542-8104
Fax: 706-542-9493
Email: rdocampo@uga.edu
Lab Homepage
Of Note
Member of the Editorial Board of Molecular and Biochemical Parasitology (1983-present), Experimental Parasitology (2005-2009), The Biochemical Journal (2005-2008) and Antimicrobial Agents and Chemotherapy (2008-present); Associate Editor of The Journal of Eukaryotic Microbiology (2004-2007); Guest Editor of Acta Tropica (2002-2005), Microscopy and Microanalysis (2004), and Experimental Parasitology (2008)
Member of Faculty of 1000 (2006-present)
Corresponding Member, Brazilian Academy of Sciences (1999-present)
Burroughs Wellcome Fund New Initiatives in Malaria Research Award (1999-2001)
Burroughs Wellcome Fund/American Society for Microbiology Visiting Professor in the Microbiological Sciences (2000-2001)
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| Acidocalcisomes (black granules) in a trypanosomatid |
Research
Our strategy is to search for metabolic pathways in parasites that
may be essential for their survival but may not find an equivalent
counterpart in the host. Currently our efforts are concentrated on the
mechanisms by which pH and calcium homeostasis are maintained by
different trypanosomatids (T. cruzi, T. brucei, and Leishmania sp.) and malaria parasites (P. falciparum, P. berghei)
and more specifically in the biochemical and molecular characterization
of a new organelle that we have discovered and named the acidocalcisome
(see figure). This organelle is acidic due to the presence of a
vacuolar H+-ATPase and a vacuolar H+-pyrophosphatase. The organelle has a Ca2+-ATPase, for Ca2+ uptake, and a Ca2+ channel, for Ca2+
release. In addition, we are studying the signaling mechanisms that
occur in the parasites and in the host cells during their interaction.
Recent developments in the study of the basic biochemistry of these
parasites have resulted in the discovery that bisphosphonates, drugs
widely used in the treatment of benign and malignant diseases
characterized by increased bone resorption, could have a role as lead
antiparasitic agents.
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| Schematic representation of a typical acidocalcisome. Ca2+ uptake occurs in exchange for H+ by a reaction catalyzed by a vacuolar Ca2+-ATPase that is inhibited by vanadate. A H+ gradient is established by a bafilomycin A1-sensitive vacuolar H+-ATPase and an aminomethylenediphosphonate (AMDP)-sensitive vacuolar H+-PPase. Ca2+ release occurs in exchange for H+ and is favored by sodium-proton exchange. An aquaporin allows water transport. Other transporters (for Mg, Zn, Fe, Pi, PPi, Arginine, Lysine, etc) are probably present. The acidocalcisome is rich in pyrophosphate, short- and long-chain polyphosphate (poly P), magnesium, calcium, sodium, and zinc. An exopolyphophatase (PPX), a pyrophosphatase (PPase) and a poly P kinase (PPK) are also present. Not all these enzymes are necessarily present in all acidocalcisomes described and their internal composition may also vary (from Docampo et al. Nat. Rev. Microbiol. 3, 251-261, 2005). |
Representative Publications
Rohloff, P., Montalvetti, A., and Docampo, R. (2004) Acidocalcisomes and the contractile vacuole are involved in osmoregulation in Trypanosoma cruzi. J. Biol. Chem. 279, 52270-52281.
Seufferheld, M., Lea, C., Vieira, M., Oldfield, E., and Docampo, R. (2004) The H+-pyrophosphatase of Rhodospirillum rubrum is predominantly located in polyphosphate-rich acidocalcisomes. J. Biol. Chem. 279, 51193-51202.
Ruiz, F. A., Lea, C. R., Oldfield, E., and Docampo, R. (2004) Human platelet dense granules contain polyphosphate and are similar to acidocalcisomes of bacteria and unicellular eukaryotes. J. Biol. Chem. 279, 44250-44257.
Montalvetti, A., Rohloff, P., and Docampo, R. (2004) A functional aquaporin co-localizes with the vacuolar proton pyrophosphatase to acidocalcisomes and the contractile vacuole complex of Trypanosoma cruzi. J. Biol. Chem. 279, 38673-38682.
Luo, S., Rohloff, P., Cox, J., Uyemura, S. A., and Docampo, R. (2004) Trypanosoma brucei plasma membrane-type Ca2+-ATPase 1 (TbPMC1) and 2 (TbPMC2) genes encode functional Ca2+-ATPases localized to the acidocalcisomes and plasma membrane, and essential for Ca2+ homeostasis and growth. J. Biol. Chem. 279, 14427-14439.
Lemercier, G., Espiau, B., Ruiz, F.A., Vieira, M., Luo, S., Baltz, T., Docampo, R., and Bakalara, N. (2004) A pyrophosphatase regulating polyphosphate metabolism in acidocalcisomes is essential for Trypanosoma brucei virulence in mice. J. Biol. Chem. 279, 3420-3425.
Uyemura, S.A., Luo, S., Vieira, M., Moreno, S.N.J., and Docampo, R. (2004) Oxidative phosphorylation and rotenone-insensitive malate- and NADH-quinone oxidoreductase in Plasmodium yoelii yoelii mitochondria in situ. J. Biol. Chem. 279, 385-393.
Docampo, R., de Souza, W., Miranda, K., Rohloff, P., and Moreno, S.N.J. (2005) Acidocalcisomes- conserved from bacteria to man. Nat. Rev. Microbiol. 3, 251-261.
Okura. M., Fang, J., Salto, M. L., Singer, R. S., Docampo, R., and Moreno, S. N. J. (2005) A lipid-modified phosphoinositide-specific phospholipase C (TcPI-PLC) is involved in differentiation of trypomastigotes to amastigotes of Trypanosoma cruzi. J. Biol. Chem. 280, 16235-16243.
Zhang, K., Hsu, F.-F., Scott, D. A., Docampo, R., Turk, J., and Beverley, S. M. (2005) Leishmania salvage and remodeling of host sphingolipids in amastigote survival and acidocalcisome biogenesis. Mol. Microbiol. 55, 1566-1578.
Vieira, M., Rohloff, P., Luo, S., Cunha-e-Silva, N., de Souza, W., and Docampo, R. (2005) Role for a P-type H+-ATPase in the acidification of the endocytic pathway of Trypanosoma cruzi. Biochem. J. 392, 467-474.
Marchesini, N., Vieira, M., Luo, S., Moreno, S. N. J., and Docampo, R. (2005) A malaria parasite-encoded vacuolar H+-ATPase is targeted to the host erythrocyte. J. Biol. Chem. 280, 36841-36847.
Gabelli, S. B., McLellan, J. S., Montalvetti, A., Oldfield, E., Docampo, R., and Amzel, L. M. (2005) Structure and mechanism of the farnesyl diphosphate synthase from Trypanosoma cruzi: implications for drug design. Proteins 62, 80-88.
Smith, S.A., Mutch, N.J., Baskar, D., Rohloff, P., Docampo, R., and Morrissey, J.H. (2006) Polyphosphate modulates blood coagulation and fibrinolysis. Proc. Natl. Acad. Sci. U.S.A., 103, 903-908.
Luo, S., Fang, J., and Docampo, R. (2006) Molecular characterization of Trypanosoma brucei P-type H+-ATPases. J. Biol. Chem. 281, 21963-21973.
Ferella, M., Montalvetti, A., Rohloff, P., Miranda, K., Fang, J., Reina, S., Kawamaki, M., Búa, J., Nilsson, D., Pravia, C., Katzin, A., Cassera, M.B., Aslund, L., Andersson, B., Docampo, R., and Bontempi, E.J. (2006) A solanesyl-diphosphate synthase localizes in glycosomes of Trypanosoma cruzi. J. Biol. Chem. 281, 39339-39348.
Fang, J., Rohloff, P., Miranda, K., and Docampo, R. (2007) Ablation of a small transmembrane protein of Trypanosoma brucei (TbVTC1) involved in the synthesis of polyphosphate alters acidocalcisome biogenesis, and leads to a cytokinesis defect. Biochem. J. 407, 161-170.
Fang, J., Ruiz, F.A., Docampo, M.D., Luo, S., Rodrigues, J.C., Motta, L.S., Rohloff, P., and Docampo, R. (2007) Overexpression of a Zn2+-sensitive soluble exopolyphosphatase from Trypanosoma cruzi depletes polyphosphate and affects osmoregulation. J. Biol. Chem. 282, 32501-32510.