title: A member of a conserved Plasmodium protein family with membrane-attack complex/perforin (MACPF)-like domains localizes to the micronemes of sporozoites.
abstract: Pore-forming proteins are employed by many pathogens to achieve successful host colonization. Intracellular pathogens use pore-forming proteins to invade host cells, survive within and productively interact with host cells, and finally egress from host cells to infect new ones. The malaria-causing parasites of the genus Plasmodium evolved a number of life cycle stages that enter and replicate in distinct cell types within the mosquito vector and vertebrate host. Despite the fact that interaction with host-cell membranes is a central theme in the Plasmodium life cycle, little is known about parasite proteins that mediate such interactions. We identified a family of five related genes in the genome of the rodent malaria parasite Plasmodium yoelii encoding secreted proteins all bearing a single membrane-attack complex/perforin (MACPF)-like domain. Each protein is highly conserved among Plasmodium species. Gene expression analysis in P. yoelii and the human malaria parasite Plasmodium falciparum indicated that the family is not expressed in the parasites blood stages. However, one of the genes was significantly expressed in P. yoelii sporozoites, the stage transmitted by mosquito bite. The protein localized to the micronemes of sporozoites, organelles of the secretory invasion apparatus intimately involved in host-cell infection. MACPF-like proteins may play important roles in parasite interactions with the mosquito vector and transmission to the vertebrate host.
authors.affiliation: Department of Pathology, Michael Heidelberger Division, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Karine
authors.initials: K
authors.lastname: Kaiser
authors.forename: Nelly
authors.initials: N
authors.lastname: Camargo
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coppens
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Morrisey
authors.forename: Akhil B
authors.initials: AB
authors.lastname: Vaidya
authors.forename: Stefan H I
authors.initials: SH
authors.lastname: Kappe
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015938:Complement Membrane Attack Complex / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017124:Conserved Sequence; D015870:Gene Expression; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D054353:Perforin; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D010967:Plasmodium yoelii / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D052899:Pore Forming Cytotoxic Proteins; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D016415:Sequence Alignment; D034101:Sporozoites / Q000235:genetics* / Q000378:metabolism
chemical_list: D015938:Complement Membrane Attack Complex; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D015800:Protozoan Proteins; D054353:Perforin