adenylyl cyclase α and camp signaling mediate plasmodium sporozoite apical regulated exocytosis and hepatocyte infection腺苷酸环化酶α和营地信号调解疟原虫子孢子顶端调节胞外分泌和肝细胞感染.pdfVIP

Adenylyl Cyclase a and cAMP Signaling Mediate Plasmodium Sporozoite Apical Regulated Exocytosis and Hepatocyte Infection 1. 1. 1 1 1 Takeshi Ono , Laura Cabrita-Santos , Ricardo Leitao , Esther Bettiol , Lisa A. Purcell , Olga Diaz- 1 2 3 4 5 1 Pulido , Lucy B. Andrews , Takushi Tadakuma , Purnima Bhanot , Maria M. Mota , Ana Rodriguez * 1 Department of Medical Parasitology, New York University School of Medicine, New York, New York, United States of America, 2 Sanaria Inc., Rockville, Maryland, United States of America, 3 Department of Parasitology and Immunology, National Defense Medical College, Tokorozawa, Saitama, Japan, 4 Department of Microbiology and Molecular Genetics, New Jersey Medical School, Newark, New Jersey, United States of America, 5 Faculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular, Lisboa, Portugal Abstract Malaria starts with the infection of the liver of the host by Plasmodium sporozoites, the parasite form transmitted by infected mosquitoes. Sporozoites migrate through several hepatocytes by breaching their plasma membranes before finally infecting one with the formation of an internalization vacuole. Migration through host cells induces apical regulated exocytosis in sporozoites. Here we show that apical regulated exocytosis is induced by increases in cAMP in sporozoites of rodent (P. yoelii and P. berghei) and human (P. falciparum) Plasmodium species. We have generated P. berghei parasites deficient in adenylyl cyclase a (ACa), a gene containing regions with high homology to adenylyl cyclases. PbACa-defic