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Dissertation
Finding the link from a surface adhesin to the actin motor for Plasmodium merozoite invasion
Doctor of Philosophy (Ph.D.), Drexel University
Aug 2008
DOI:
https://doi.org/10.17918/00009574
Abstract
Malaria parasite invasion involves the linkage between the host cell being invaded and the actin-myosin motor of the parasite that drives the invasion. In sporozoites, the hepatocyte invading stage of the parasite, this function is completed by Thrombospondin Related Anonymous Protein (TRAP), which links the host cell being invaded to the actin-myosin motor via an indirect linkage requiring parasite aldolase. However, the nature of the molecule(s) that perform(s) this function in the blood stage of the parasite is less studied. Based on previous research, Plasmodium TRAP has been characterized as a Type I transmemberane protein. Its extracellular domain contains the von Willebrand factor A (A domain) and thrombospondin type I (TSP1) domains, which are involved in the host cell binding function. TRAP has a short cytoplasmic tail, which is acidic in nature, and has a conserved tryptophan residue close to the carboxy-terminus. We have identified and characterized two additional molecules through a bioinformatic approach using the completed P. falciparum genome sequence and the sequence characteristics of TRAP. These molecules are denoted MTRAP (Merozoite TRAP-like molecule), and TLP (TRAP- Like Protein). To characterize these two molecules, we have performed aldolase binding assays, red blood cell (RBC) binding assays, gene knockout studies, and immunization/protection assays for both molecules. Also for MTRAP, we performed microarray studies and real-time PCR to compare the different gene expression mRNA patterns in the wild type (WT) and the MTRAP knockout (KO) parasites. In conclusion, we have found that both molecules bind to aldolase in vitro, but not to RBCs in vitro. Gene knockout studies have shown that both molecules were nonessential, although the invasion ability of the KO parasites was altered from that of the WT parasite. Immunization with either molecule has not generated a protective response in mice upon subsequent parasite challenge. Interestingly, for MTRAP, the microarray studies show that many invasion-related molecules were significantly upregulated in the MTRAP KO parasites.
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Details
- Title
- Finding the link from a surface adhesin to the actin motor for Plasmodium merozoite invasion
- Creators
- Hui Nie
- Contributors
- Lawrence W. Bergman (Advisor) - Drexel University, Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- x, 146 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 991021889099504721