The Central Role of cAMP in Regulating Plasmodium falciparum Merozoite Invasion of Human Erythrocytes

Amrita Dawn1., Shailja Singh1,2., Kunal R. More1", Faiza Amber Siddiqui1", Niseema Pachikara1, Ghania Ramdani3, Gordon Langsley3, Chetan E. Chitnis1,2*

PLOS Pathogens Dec 18, 2014

Speaker: Po-Liang,Chu (朱珀亮)                                 Time: 14:00~15:00, Dec 30 2015

Commentator: Dr. Chih-Li,Hsu (胥直利 老師)         Place: Room 601

Abstract:

        Malaria is a mosquito-borne infectious disease of humans and other animals caused by parasitic protozoans. Malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. The blood stage of malaria parasites is responsible for all the morbidity and mortality associated with malaria. Invasion of erythrocytes by P. falciparum merozoites is a complex multi-step process that is mediated by specific molecular interactions between red cell surface receptors and parasite protein ligands.[1] Timely secretion of these parasite ligands(Microneme) to themerozoite surface is critical for successful invasion.[2] The authors demonstrate that cAMP serves as a key second messenger that controls the timely secretion of microneme(Mn)AMA1 proteins during invasion. They show that exposure of merozoites to a low K+ environment, as found in blood plasma, leads to a rise in cytosolic cAMP levels due to activation of the cytoplasmic, adenylyl cyclase b (PfACb). A rise in cAMP activates protein kinase A (PKA), which regulates Mn secretion. They also show that cAMP regulates merozoite cytosolic Ca2+ levels via induction of an Epacpathway. The pathway activates Rap1.Rap1 thus induces Phospholipase C(PLC) and lead to a rise in cytosolic Ca2+. They demonstrate that increases in both cAMP and Ca2+ are essential to trigger Mn secretion. They also identify the different material,like KH7,ACTZ and ESI-09 that regulateMn secretion during invasion provides novel targets to block erythrocyte invasion, inhibit blood stage parasite growth and prevent malaria.

Reference:

1.     Cowman AF, Crabb BS. (2006) Invasion of red blood cells by malaria parasites. Cell 124: 755–766.

2.     Sharma P, Chitnis CE. (2013) Key molecular events during host cell invasion by Apicomplexan pathogens. Curr Opin Microbiol 16: 432–437.