Invasion of Erythrocytes by Malarial Merozoites

Abstract

The first step in invasion of an erythrocyte by a malarial merozoite is attachment of the merozoite to the erythrocyte surface. This initial attachment can occur via any part of the merozoite's surface, but for the subsequent steps of invasion, the attached merozoite must reorient its apical end towards the erythrocyte. Following reorientation, three things happen: (1) apical organelles known as the rhoptries begin to discharge their contents onto the erythrocyte surface; (2) the erythrocyte experiences one or more transient surface deformations; and (3) a region of tight apposition, or junction, develops between the membranes of the two cells. A thin layer of electron-dense material is seen beneath the inner leaflet of the erythrocyte membrane bilayer at the junction. An indentation forms in the erythrocyte surface at the point of contact between the two cells, and the junction transforms from a localized patch to a diaphragm-like ring, through which the merozoite penetrates into a progressively deepening, membrane-bound parasitophorous vacuole. The filamentous surface coat of the merozoite is progressively stripped off as the merozoite is internalized. Once the merozoite is completely inside the erythrocyte (10-20 s after penetration starts), the junction pinches closed, the erythrocyte membrane fuses with itself, and the parsite finds itself completely surrounded by the parasitophorous vacuole membrane, or PVM, within which it grows and divides to produce the next generation of invasive merozoites. While the multiple steps involved in invasion have been well characterized morphologically, we know much less about the molecular mechanisms underlying this phenomenology. The purpose of this review is to summarize what is currently known about the mechanisms underlying invasion, and to identify some of the outstanding questions that remain to be solved.