title: Temporal evaluation of commitment to sexual development in Plasmodium falciparum.
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 α(s) class of heterotrimeric G protein α subunits in mammalian systems has been reported to detect a number of G(α) 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 Gas and Gai/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Malaria Biology Laboratory, Queensland Institute of Medical Research, 300 Herston Rd, Herston, QLD 4006, Australia.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Peatey
authors.forename: Matthew W A
authors.initials: MW
authors.lastname: Dixon
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gardiner
authors.forename: Katharine R
authors.initials: KR
authors.lastname: Trenholme
mesh_terms: D002772:Cholera Toxin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides / Q000378:metabolism; D010963:Plasmodium falciparum / Q000166:cytology* / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D015800:Protozoan Proteins / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C084070:Mas7 protein, synthetic; D010455:Peptides; D015800:Protozoan Proteins; D002772:Cholera Toxin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins