Tags

Type your tag names separated by a space and hit enter

Essential role of membrane-attack protein in malarial transmission to mosquito host.
Proc Natl Acad Sci U S A. 2004 Nov 16; 101(46):16310-5.PN

Abstract

After ingestion of infected blood by a mosquito, malarial parasites are fertilized in the mosquito midgut and develop into motile ookinetes. These ookinetes invade epithelial cells by rupturing the cell membrane and migrate through the cytoplasm toward the basal lamina, on which they develop to oocysts. Here we report that a microneme protein with a membrane-attack complex and perforin (MACPF)-related domain, which we name membrane-attack ookinete protein (MAOP), is produced in the ookinete stage and plays an essential role in midgut invasion by the ookinete. Ookinetes with the MAOP gene disrupted completely lost infectivity to the midgut. After ingestion of blood infected with the disrupted parasite, the midgut epithelium remained intact, making a clear contrast with the damaged midgut epithelium invaded by wild-type ookinetes. Electron microscopic analysis showed that the disruptant ookinetes migrate to the gut epithelium and attach to the cell surface at the apical tip, but are unable to enter the cytoplasm by rupturing the cell membrane. These results indicate that the MAOP molecule acts on the plasma membrane of the host-cell-like mammalian MACPF family proteins that create pores in the membrane of target cells. Another previously identified MACPF-related molecule is produced in the liver-infective sporozoite and has a crucial role in traversing the liver sinusoidal cell boundary. The present finding, thus, suggests that conserved mechanisms for membrane rupture involving MACPF-related proteins are used in different host invasive stages of the malarial parasite, playing a key role in breaching biological barriers of host organs.

Authors+Show Affiliations

Mie University School of Medicine, Mie 514-0001, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15520375

Citation

Kadota, Kimie, et al. "Essential Role of Membrane-attack Protein in Malarial Transmission to Mosquito Host." Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 46, 2004, pp. 16310-5.
Kadota K, Ishino T, Matsuyama T, et al. Essential role of membrane-attack protein in malarial transmission to mosquito host. Proc Natl Acad Sci USA. 2004;101(46):16310-5.
Kadota, K., Ishino, T., Matsuyama, T., Chinzei, Y., & Yuda, M. (2004). Essential role of membrane-attack protein in malarial transmission to mosquito host. Proceedings of the National Academy of Sciences of the United States of America, 101(46), 16310-5.
Kadota K, et al. Essential Role of Membrane-attack Protein in Malarial Transmission to Mosquito Host. Proc Natl Acad Sci USA. 2004 Nov 16;101(46):16310-5. PubMed PMID: 15520375.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Essential role of membrane-attack protein in malarial transmission to mosquito host. AU - Kadota,Kimie, AU - Ishino,Tomoko, AU - Matsuyama,Takahiro, AU - Chinzei,Yasuo, AU - Yuda,Masao, Y1 - 2004/11/01/ PY - 2004/11/3/pubmed PY - 2004/12/28/medline PY - 2004/11/3/entrez SP - 16310 EP - 5 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 101 IS - 46 N2 - After ingestion of infected blood by a mosquito, malarial parasites are fertilized in the mosquito midgut and develop into motile ookinetes. These ookinetes invade epithelial cells by rupturing the cell membrane and migrate through the cytoplasm toward the basal lamina, on which they develop to oocysts. Here we report that a microneme protein with a membrane-attack complex and perforin (MACPF)-related domain, which we name membrane-attack ookinete protein (MAOP), is produced in the ookinete stage and plays an essential role in midgut invasion by the ookinete. Ookinetes with the MAOP gene disrupted completely lost infectivity to the midgut. After ingestion of blood infected with the disrupted parasite, the midgut epithelium remained intact, making a clear contrast with the damaged midgut epithelium invaded by wild-type ookinetes. Electron microscopic analysis showed that the disruptant ookinetes migrate to the gut epithelium and attach to the cell surface at the apical tip, but are unable to enter the cytoplasm by rupturing the cell membrane. These results indicate that the MAOP molecule acts on the plasma membrane of the host-cell-like mammalian MACPF family proteins that create pores in the membrane of target cells. Another previously identified MACPF-related molecule is produced in the liver-infective sporozoite and has a crucial role in traversing the liver sinusoidal cell boundary. The present finding, thus, suggests that conserved mechanisms for membrane rupture involving MACPF-related proteins are used in different host invasive stages of the malarial parasite, playing a key role in breaching biological barriers of host organs. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/15520375/Essential_role_of_membrane_attack_protein_in_malarial_transmission_to_mosquito_host_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=15520375 DB - PRIME DP - Unbound Medicine ER -