Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite.
Transmission of malaria parasites to mosquitoes is initiated by the obligatory sexual reproduction of the parasite within the mosquito bloodmeal. Differentiation of specialized transmission stages, the gametocytes, into male and female gametes is induced by a small mosquito molecule, xanthurenic acid (XA). Using a Plasmodium berghei strain expressing a bioluminescent calcium sensor, we show that XA triggers a rapid rise in cytosolic calcium specifically in gametocytes that is essential for their differentiation into gametes. A member of a family of plant-like calcium dependent protein kinases, CDPK4, is identified as the molecular switch that translates the XA-induced calcium signal into a cellular response by regulating cell cycle progression in the male gametocyte. CDPK4 is shown to be essential for the sexual reproduction and mosquito transmission of P. berghei. This study reveals an unexpected function for a plant-like signaling pathway in cell cycle regulation and life cycle progression of a malaria parasite.
Billker
Oliver
O
Department of Biological Sciences, Imperial College London, London SW7 2AZ, United Kingdom. o.billker@imperial.ac.uk
Dechamps
Sandrine
S
Tewari
Rita
R
Wenig
Gerald
G
Franke-Fayard
Blandine
B
Brinkmann
Volker
V
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D009033:Culicidae / Q000469:parasitology; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005260:Female; D005407:Flagella / Q000201:enzymology / Q000648:ultrastructure; D005854:Germ Cells / Q000201:enzymology* / Q000254:growth & development / Q000648:ultrastructure; D006790:Host-Parasite Interactions / Q000502:physiology; D008297:Male; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010940:Plant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010962:Plasmodium berghei / Q000201:enzymology* / Q000254:growth & development / Q000648:ultrastructure; D011494:Protein Kinases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D012098:Reproduction / Q000235:genetics*; D016196:S Phase / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D014977:Xanthurenates / Q000378:metabolism
D018076:DNA, Complementary; D010940:Plant Proteins; D014977:Xanthurenates; C028330:xanthurenic acid; D011494:Protein Kinases; D002118:Calcium