Skip to main content
Top
Published in: Malaria Journal 1/2013

Open Access 01-12-2013 | Research

Temporal evaluation of commitment to sexual development in Plasmodium falciparum

Authors: Christopher L Peatey, Matthew WA Dixon, Donald L Gardiner, Katharine R Trenholme

Published in: Malaria Journal | Issue 1/2013

Login to get access

Abstract

Background

The production of gametocytes is essential for transmission of malaria parasites from the mammalian host to the mosquito vector. However the process by which the asexual blood-stage parasite undergoes commitment to sexual development is not well understood. This process is known to be sensitive to environmental stimuli and it has been suggested that a G protein dependent system may mediate the switch, but there is little evidence that the Plasmodium falciparum genome encodes heterotrimeric G proteins. Previous studies have indicated that the malaria parasite can interact with endogenous erythrocyte G proteins, and other components of the cyclic nucleotide pathway have been identified in P. falciparum. Also, the polypeptide cholera toxin, which induces commitment to gametocytogenesis is known to catalyze the ADP-ribosylation of the αs class of heterotrimeric G protein α subunits in mammalian systems has been reported to detect a number of Gα subunits in P. falciparum- infected red cells.

Methods

Cholera toxin and Mas 7 (a structural analogue of Mastoparan) were used to assess the role played by putative G protein signalling in the commitment process, both are reported to interact with different components of classical Gαs and Gαi/o signalling pathways. Their ability to induce gametocyte production in the transgenic P. falciparum line Pfs16-GFP was determined and downstream effects on the secondary messenger cAMP measured.

Results

Treatment of parasite cultures with either cholera toxin or MAS 7 resulted in increased gametocyte production, but only treatment with MAS 7 resulted in a significant increase in cAMP levels. This indicates that MAS 7 acts either directly or indirectly on the P. falciparum adenylyl cyclase.

Conclusion

The observation that cholera toxin treatment did not affect cAMP levels indicates that while addition of cholera toxin does increase gametocytogenesis the method by which it induces increased commitment is not immediately obvious, except that is unlikely to be via heterotrimeric G proteins.
Appendix
Available only for authorised users
Literature
1.
go back to reference Talman AM, Domarle O, McKenzie FE, Ariey F, Robert V: Gametocytogenesis: the puberty of Plasmodium falciparum. Malar J. 2004, 3: 24-10.1186/1475-2875-3-24.PubMedCentralCrossRefPubMed Talman AM, Domarle O, McKenzie FE, Ariey F, Robert V: Gametocytogenesis: the puberty of Plasmodium falciparum. Malar J. 2004, 3: 24-10.1186/1475-2875-3-24.PubMedCentralCrossRefPubMed
2.
go back to reference Schneweis S, Maier WA, Seitz HM: Haemolysis of infected erythrocytes-a trigger for formation of P. falciparum gametocytes?. Parasitol Res. 1991, 77: 458-460. 10.1007/BF00931646.CrossRefPubMed Schneweis S, Maier WA, Seitz HM: Haemolysis of infected erythrocytes-a trigger for formation of P. falciparum gametocytes?. Parasitol Res. 1991, 77: 458-460. 10.1007/BF00931646.CrossRefPubMed
3.
go back to reference Williams JL: Stimulation of Plasmodium falciparum gametocytogenesis by conditioned medium from parasite cultures. AmJTrop Med Hyg. 1999, 60: 7-13. Williams JL: Stimulation of Plasmodium falciparum gametocytogenesis by conditioned medium from parasite cultures. AmJTrop Med Hyg. 1999, 60: 7-13.
4.
go back to reference Trager W, Gill GS: Plasmodium falciparum gametocyte formation invitro—its stimulation by phorbol diesters and by 8-bromo cyclic adenosinemonophosphate. J Protozool. 1989, 36: 451-454.CrossRefPubMed Trager W, Gill GS: Plasmodium falciparum gametocyte formation invitro—its stimulation by phorbol diesters and by 8-bromo cyclic adenosinemonophosphate. J Protozool. 1989, 36: 451-454.CrossRefPubMed
5.
go back to reference Dyer M, Day K: Expression of P. falciparum trimeric G proteins and their involvement in switching to sexual development. Mol Biochem Parasitol. 2000, 110: 437-48. 10.1016/S0166-6851(00)00288-7.CrossRefPubMed Dyer M, Day K: Expression of P. falciparum trimeric G proteins and their involvement in switching to sexual development. Mol Biochem Parasitol. 2000, 110: 437-48. 10.1016/S0166-6851(00)00288-7.CrossRefPubMed
6.
go back to reference Dixon MW, Thompson J, Gardiner DL, Trenholme KR: Sex in Plasmodium – a sign of commitment. Trends Parasitol. 2008, 24: 168-75. 10.1016/j.pt.2008.01.004.CrossRefPubMed Dixon MW, Thompson J, Gardiner DL, Trenholme KR: Sex in Plasmodium – a sign of commitment. Trends Parasitol. 2008, 24: 168-75. 10.1016/j.pt.2008.01.004.CrossRefPubMed
7.
go back to reference Neves SR, Ram PT, Iyengar R: G protein pathways. Science. 2002, 296: 1636-1639. 10.1126/science.1071550.CrossRefPubMed Neves SR, Ram PT, Iyengar R: G protein pathways. Science. 2002, 296: 1636-1639. 10.1126/science.1071550.CrossRefPubMed
8.
go back to reference Edelman AM, Blumenthal DK, Krebs EG: Protein serine/threonine kinases. Ann Rev Biochem. 1987, 56: 567-613. 10.1146/annurev.bi.56.070187.003031.CrossRefPubMed Edelman AM, Blumenthal DK, Krebs EG: Protein serine/threonine kinases. Ann Rev Biochem. 1987, 56: 567-613. 10.1146/annurev.bi.56.070187.003031.CrossRefPubMed
9.
go back to reference Baker D: Cyclic nucleotide signalling in malaria parasites. Cell Micro. 2011, 13: 331-10.1111/j.1462-5822.2010.01561.x.CrossRef Baker D: Cyclic nucleotide signalling in malaria parasites. Cell Micro. 2011, 13: 331-10.1111/j.1462-5822.2010.01561.x.CrossRef
10.
go back to reference Murphy SC, Harrison T, Hamm HE, Lomasney JW, Mohandas N, Haldar K: Erythrocyte G protein as a novel target for malarial chemotherapy. PLoS Med. 2006, 12: e528-CrossRef Murphy SC, Harrison T, Hamm HE, Lomasney JW, Mohandas N, Haldar K: Erythrocyte G protein as a novel target for malarial chemotherapy. PLoS Med. 2006, 12: e528-CrossRef
11.
go back to reference Harrison T, Samuel BU, Akompong T, Hamm H, Mohandas N, Lomasney JW, Haldar K: Erythrocyte G protein-coupled receptor signalling in malarial infection. Science. 2003, 301: 1734-1736. 10.1126/science.1089324.CrossRefPubMed Harrison T, Samuel BU, Akompong T, Hamm H, Mohandas N, Lomasney JW, Haldar K: Erythrocyte G protein-coupled receptor signalling in malarial infection. Science. 2003, 301: 1734-1736. 10.1126/science.1089324.CrossRefPubMed
12.
go back to reference Liu Z, Miao J, Cui L: Gametocytogenesis in malaria parasite: commitment, development and regulation. Future Microbiol. 2011, 6: 1351-1369. 10.2217/fmb.11.108.CrossRefPubMed Liu Z, Miao J, Cui L: Gametocytogenesis in malaria parasite: commitment, development and regulation. Future Microbiol. 2011, 6: 1351-1369. 10.2217/fmb.11.108.CrossRefPubMed
13.
go back to reference Thelu J, Bracchi V, Burnod J, Ambroise-Thomas P: Evidence for expression of a Ras-like and a stage specific GTP binding homologous protein by Plasmodium falciparum. Cell Signal. 1994, 6: 777-782. 10.1016/0898-6568(94)00038-7.CrossRefPubMed Thelu J, Bracchi V, Burnod J, Ambroise-Thomas P: Evidence for expression of a Ras-like and a stage specific GTP binding homologous protein by Plasmodium falciparum. Cell Signal. 1994, 6: 777-782. 10.1016/0898-6568(94)00038-7.CrossRefPubMed
14.
go back to reference Higashijima T, Burnier J, Ross EM: Regulation of Gi and Go by mastoparan, related amphiphilic peptides, and hydrophobic amines - mechanism and structural determinants of activity. J Biol Chem. 1990, 265: 14176-14186.PubMed Higashijima T, Burnier J, Ross EM: Regulation of Gi and Go by mastoparan, related amphiphilic peptides, and hydrophobic amines - mechanism and structural determinants of activity. J Biol Chem. 1990, 265: 14176-14186.PubMed
15.
go back to reference Kongkasuriyachai D, Kumar N: Functional characterisation of sexual stage specific proteins in P. falciparum. Int J Parasitol. 2002, 32: 1559-1566. 10.1016/S0020-7519(02)00184-4.CrossRefPubMed Kongkasuriyachai D, Kumar N: Functional characterisation of sexual stage specific proteins in P. falciparum. Int J Parasitol. 2002, 32: 1559-1566. 10.1016/S0020-7519(02)00184-4.CrossRefPubMed
16.
go back to reference Kongkasuriyachai D, Fujioka H, Kumar N: Functional analysis of Plasmodium falciparum parasitophorous vacuole membrane protein (Pfs16) during gametocytogenesis and gametogenesis by targeted gene disruption. Mol Biochem Parasitol. 2004, 133: 275-285. 10.1016/j.molbiopara.2003.10.014.CrossRefPubMed Kongkasuriyachai D, Fujioka H, Kumar N: Functional analysis of Plasmodium falciparum parasitophorous vacuole membrane protein (Pfs16) during gametocytogenesis and gametogenesis by targeted gene disruption. Mol Biochem Parasitol. 2004, 133: 275-285. 10.1016/j.molbiopara.2003.10.014.CrossRefPubMed
17.
go back to reference Dixon MWA, Peatey CL, Gardiner DL, Trenholme KR: A green fluorescent protein-based assay for determining gametocyte production in Plasmodium falciparum. Mol Biochem Parasitol. 2009, 163: 123-126. 10.1016/j.molbiopara.2008.10.004.CrossRefPubMed Dixon MWA, Peatey CL, Gardiner DL, Trenholme KR: A green fluorescent protein-based assay for determining gametocyte production in Plasmodium falciparum. Mol Biochem Parasitol. 2009, 163: 123-126. 10.1016/j.molbiopara.2008.10.004.CrossRefPubMed
18.
go back to reference Dearnley MK, Yeoman JA, Hanssen E, Kenny S, Turnbull L, Whitchurch CB, Tilley L, Dixon MW: Origin, composition, organization and function of the inner membrane complex of Plasmodium falciparum gametocytes. J Cell Sci. 2012, 125: 2053-2063. 10.1242/jcs.099002.CrossRefPubMed Dearnley MK, Yeoman JA, Hanssen E, Kenny S, Turnbull L, Whitchurch CB, Tilley L, Dixon MW: Origin, composition, organization and function of the inner membrane complex of Plasmodium falciparum gametocytes. J Cell Sci. 2012, 125: 2053-2063. 10.1242/jcs.099002.CrossRefPubMed
19.
go back to reference Bruce MC, Alano P, Duthie S, Carter R: Commitment of the malaria parasite Plasmodium falciparum to sexual and asexual development. Parasitology. 1990, 100: 191-200. 10.1017/S0031182000061199.CrossRefPubMed Bruce MC, Alano P, Duthie S, Carter R: Commitment of the malaria parasite Plasmodium falciparum to sexual and asexual development. Parasitology. 1990, 100: 191-200. 10.1017/S0031182000061199.CrossRefPubMed
20.
go back to reference Kirk K, Horner HA, Elford BC, Ellory JC, Newbold CI: Transport of diverse substrates into malaria-infected erythrocytes via a pathway showing functional characteristics of a chloride channel. J Biol Chem. 1994, 269: 3339-3347.PubMed Kirk K, Horner HA, Elford BC, Ellory JC, Newbold CI: Transport of diverse substrates into malaria-infected erythrocytes via a pathway showing functional characteristics of a chloride channel. J Biol Chem. 1994, 269: 3339-3347.PubMed
21.
go back to reference Kutner S, Breuer WV, Ginsburg H, Aley SB, Cabantchik ZI: Characterization of permeation pathways in the plasma membrane of human erythrocytes infected with early stages of Plasmodium falciparum: association with parasite development. J Cell Physiol. 1985, 125: 521-527. 10.1002/jcp.1041250323.CrossRefPubMed Kutner S, Breuer WV, Ginsburg H, Aley SB, Cabantchik ZI: Characterization of permeation pathways in the plasma membrane of human erythrocytes infected with early stages of Plasmodium falciparum: association with parasite development. J Cell Physiol. 1985, 125: 521-527. 10.1002/jcp.1041250323.CrossRefPubMed
22.
go back to reference Kaushal DC, Carter R, Miller LH, Krishna G: Gametocytogenesis by malaria parasites in continuous culture. Nature. 1980, 286: 490-492. 10.1038/286490a0.CrossRefPubMed Kaushal DC, Carter R, Miller LH, Krishna G: Gametocytogenesis by malaria parasites in continuous culture. Nature. 1980, 286: 490-492. 10.1038/286490a0.CrossRefPubMed
23.
go back to reference Inselburg J: Stage-specific inhibitory effect of cyclic AMP on asexual maturation and gametocyte formation of Plasmodium falciparum. J Parasitol. 1983, 69: 592-597. 10.2307/3281375.CrossRefPubMed Inselburg J: Stage-specific inhibitory effect of cyclic AMP on asexual maturation and gametocyte formation of Plasmodium falciparum. J Parasitol. 1983, 69: 592-597. 10.2307/3281375.CrossRefPubMed
24.
go back to reference Brockleman CR: Conditions favouring gametocytogenesis in the continuous culture of Plasmodium falciparum. J Protozool. 1982, 29: 454-458.CrossRef Brockleman CR: Conditions favouring gametocytogenesis in the continuous culture of Plasmodium falciparum. J Protozool. 1982, 29: 454-458.CrossRef
25.
go back to reference Read LK, Mikklesen RB: Comparison of adenylate cyclase and cAMP-dependent protein kinase in gametocytogenic and nongametocytogenic clones of Plasmodium falciparum. J Parasitol. 1991, 77: 346-352.CrossRefPubMed Read LK, Mikklesen RB: Comparison of adenylate cyclase and cAMP-dependent protein kinase in gametocytogenic and nongametocytogenic clones of Plasmodium falciparum. J Parasitol. 1991, 77: 346-352.CrossRefPubMed
26.
go back to reference Sprague R, Bowles E, Stumpf M, Ricketts G, Freidman A, Hou WH, Stephenson A, Lonigro A: Rabbit erythrocytes possess adenylyl cyclase type II that is activated by the heterotrimeric G proteins Gs and Gi. Pharmacol Rep. 2005, 57: 222-228.PubMed Sprague R, Bowles E, Stumpf M, Ricketts G, Freidman A, Hou WH, Stephenson A, Lonigro A: Rabbit erythrocytes possess adenylyl cyclase type II that is activated by the heterotrimeric G proteins Gs and Gi. Pharmacol Rep. 2005, 57: 222-228.PubMed
27.
go back to reference Olearczyk JJ, Stephenson AH, Lonigro AJ, Sprague RS: Olearczyk: Heterotrimeric G protein Gi is involved in a signal transduction pathway for ATP release from erythrocytes. Am J Physiol Heart Circ Physiol. 2004, 286: 940-945.CrossRef Olearczyk JJ, Stephenson AH, Lonigro AJ, Sprague RS: Olearczyk: Heterotrimeric G protein Gi is involved in a signal transduction pathway for ATP release from erythrocytes. Am J Physiol Heart Circ Physiol. 2004, 286: 940-945.CrossRef
28.
go back to reference Sprague RS, Stephenson AH, Bowles EA, Stumpf MS, Lonigro AJ: Reduced expression of G(i) in erythrocytes of humans with type 2 diabetes is associated with impairment of both cAMP generation and ATP release. Diabetes. 2006, 55: 3588-3593. 10.2337/db06-0555.CrossRefPubMed Sprague RS, Stephenson AH, Bowles EA, Stumpf MS, Lonigro AJ: Reduced expression of G(i) in erythrocytes of humans with type 2 diabetes is associated with impairment of both cAMP generation and ATP release. Diabetes. 2006, 55: 3588-3593. 10.2337/db06-0555.CrossRefPubMed
29.
30.
go back to reference Ono T, Cabrita-Santos L, Leitao R, Bettiol E, Purcell LA, Diaz-Pulido O, Andrews LB, Tadakuma T, Bhanot P, Mota MM, Rodriguez A: Adenylyl cyclase alpha and cAMP signaling mediate Plasmodium sporozoite apical regulated exocytosis and hepatocyte infection. PLoS Pathog. 2008, 29 (4): e1000008-CrossRef Ono T, Cabrita-Santos L, Leitao R, Bettiol E, Purcell LA, Diaz-Pulido O, Andrews LB, Tadakuma T, Bhanot P, Mota MM, Rodriguez A: Adenylyl cyclase alpha and cAMP signaling mediate Plasmodium sporozoite apical regulated exocytosis and hepatocyte infection. PLoS Pathog. 2008, 29 (4): e1000008-CrossRef
31.
go back to reference Kebaier C, Vanderberg JP: Initiation of Plasmodium sporozoite motility by albumin is associated with induction of intracellular signalling. Int J Parasitol. 2010, 40: 25-33. 10.1016/j.ijpara.2009.06.011.PubMedCentralCrossRefPubMed Kebaier C, Vanderberg JP: Initiation of Plasmodium sporozoite motility by albumin is associated with induction of intracellular signalling. Int J Parasitol. 2010, 40: 25-33. 10.1016/j.ijpara.2009.06.011.PubMedCentralCrossRefPubMed
32.
go back to reference Maenz DD, Forsyth GW: Cholera toxin facilitates calcium transport in jejunal brush border vesicles. Can J Physiol Pharmacol. 1986, 64: 568-574. 10.1139/y86-094.CrossRefPubMed Maenz DD, Forsyth GW: Cholera toxin facilitates calcium transport in jejunal brush border vesicles. Can J Physiol Pharmacol. 1986, 64: 568-574. 10.1139/y86-094.CrossRefPubMed
Metadata
Title
Temporal evaluation of commitment to sexual development in Plasmodium falciparum
Authors
Christopher L Peatey
Matthew WA Dixon
Donald L Gardiner
Katharine R Trenholme
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2013
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-12-134

Other articles of this Issue 1/2013

Malaria Journal 1/2013 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.