Invasion of host cells by malaria parasites: a tale of two protein families

Abstract

SummaryMalaria parasites are obligate intracellular parasites whose invasive stages select and invade the unique host cell in which they can develop with exquisite specificity and efficacy. Most studies aimed at elucidating the molecules and the mechanisms implicated in the selection and invasion processes have been conducted on the merozoite, the stage that invades erythrocytes to perpetuate the pathological cycles of parasite multiplication in the blood. Bioinformatic analysis has helped identify the members of two parasite protein families, the reticulocyte-binding protein homologues (RBL) and erythrocyte binding like (EBL), in recently sequenced genomes of different Plasmodium species. In this article we review data from classical studies and gene disruption experiments that are helping to illuminate the role of these proteins in the selection-invasion processes. The manner in which subsets of proteins from each of the families act in concert suggests a model to explain the ability of the parasites to use alternate pathways of invasion. Future perspectives and implications are discussed.

Gene encoding erythrocyte binding ligand linked to blood stage multiplication rate phenotype inPlasmodium yoelii yoelii

“…These proteins share significant similarity to the P. vivax reticulocyte-binding protein 2 (26) and also have some similarity with a 500-residue region within the C terminus of the 235-kDa family of rhoptry proteins of P. yoelii (Py235) (26). It has recently been proposed that the differences in erythrocyte invasion preference in the fast-multiplying (virulent) and slowmultiplying (avirulent) lines of P. y. yoelii and, by implication, therefore, in their blood stage multiplication rate differences, could be associated with differences in expression of members of the Py235 multigene family which encode the 235-kDa rhoptry proteins (18,27). Iyer and colleagues (28) have reported increased expression of specific Py235 genes during blood infections of 17XYM that coincide with the time of sudden change from slow to rapid multiplication rate that characterizes this parasite line and phenotype.…”

“…Proteins that are the expression products of several distinct gene families of malaria parasites have been implicated in erythrocyte invasion processes (18). Genetically based structural differences (polymorphisms) in these proteins might be expected to affect the rate of multiplication of the parasites in the blood of a host.…”

Biology of Malaria Parasites

“…However, much still remains to be learned about the cellular and molecular biology of merozoite invasion. [ 73,74 ] …”

In Silico Characterization of Plasmodium falciparum and P. yoelii Translocon and Exoribonuclease II (RNase II) Identified in the Merozoite Rhoptry Proteome

“…Genomic and proteomic studies of Plasmodium asexual stages and merozoite rhoptries [15][16][17] generated large amounts of data demonstrating conservation of genes encoding proteins with potential involvement in establishing the early stages of parasitism in asexual stage parasite development within the host erythrocyte. In addition, proteins involved in erythrocyte invasion were identified [13,17]. Two rhoptry genes were selected for further characterization in this study; the RNAse II gene (PF3D7_0906000) and the Translocon gene (PF3D7_1436300).…”

“…The disease affects about 219 million people with an estimated 660,000 deaths [1,2]. Host erythrocyte invasion by the Plasmodium merozoite is dynamic and is mediated by ligandreceptor interactions involving Plasmodium rhoptry neck and body proteins [3][4][5][6] as well as microneme proteins, leading to a moving junction formation that assists merozoite entry into the erythrocyte [7][8][9][10][11][12][13][14]. Genomic and proteomic studies of Plasmodium asexual stages and merozoite rhoptries [15][16][17] generated large amounts of data demonstrating conservation of genes encoding proteins with potential involvement in establishing the early stages of parasitism in asexual stage parasite development within the host erythrocyte.…”