Author:
Akhouri Reetesh Raj,Sharma Ashwani,Malhotra Pawan,Sharma Amit
Abstract
Abstract
Background
Thrombospondin-related anonymous protein (TRAP) is essential for sporozoite motility and for liver cell invasion. TRAP is a type 1 membrane protein that possesses multiple adhesive domains in its extracellular region.
Methods
Plasmodium falciparum TRAP (PfTRAP) and its subdomains were expressed in a mammalian expression system, and eleven different mutants generated to study interaction of PfTRAP with liver cells. Binding studies between HepG2 cell extracts and PfTRAP were performed using co-immunoprecipitation protocols.
Results
Five different amino acid residues of PfTRAP that are involved in liver cell binding have been identified. These PfTRAP mutants bound to heparin like the wild type PfTRAP thereby suggesting a non-heparin mediated binding of PfTRAP to liver cells. Three Src family proteins -Lyn, Lck and CrkL which interact with PfTRAP are also identified. Liver cell extracts and immunoprecipitated Src family kinases phosphorylated PfTRAP at multiple sites. An analysis of multiple TRAP sequences revealed Src homology 3 domain (SH3) binding motifs.
Conclusion
Binding of PfTRAP to SH3-domain containing proteins like Src-family kinases and their ability to phosphorylate PfTRAP suggests a novel role for PfTRAP in cell signaling during sporozoite invasion and homing inside the liver cells. These data shed new light on TRAP-liver cell interactions.
Publisher
Springer Science and Business Media LLC
Subject
Infectious Diseases,Parasitology
Reference32 articles.
1. Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI: The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature. 2005, 434: 214-217. 10.1038/nature03342.
2. Morrissette NS, Sibley LD: Cytoskeleton of apicomplexan parasites. Microbiol Mol Biol Rev. 2002, 66: 21-38. 10.1128/MMBR.66.1.21-38.2002.
3. Soldati D, Meissner M: Toxoplasma as a novel system for motility. Curr Opin Cell Biol. 2004, 16: 32-40. 10.1016/j.ceb.2003.11.013.
4. Carruthers VB, Sibley LD: Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts. Eur J Cell Biol. 1997, 73: 114-23.
5. Cerami C, Frevert U, Sinnis P, Takacs B, Clavijo P, Santos MJ, Nussenzweig V: The basolateral domain of the hepatocyte plasma membrane bears receptors for the circumsporozoite protein of Plasmodium falciparum sporozoites. Cell. 1992, 70: 1021-1033. 10.1016/0092-8674(92)90251-7.
Cited by
28 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献