The moving junction, a key portal to host cell invasion by apicomplexan parasites

Abstract

One defining feature of apicomplexan parasites is their special ability to actively invade host cells. Although rapid, invasion is a complicated process that requires coordinated activities of host cell attachment, protein secretion, and motility by the parasite. Central to this process is the establishment of a structure called moving junction (MJ), which forms a tight connection between invading parasite and host cell membranes through which the parasite passes to enter into the host. Although recognized microscopically for decades, molecular characterization of the MJ was only enabled by the recent discovery of components that make up this multi-protein complex. Exciting progress made during the past few years on both the structure and function of the components of the MJ is reviewed here.

Fig 1

Molecular details of the moving junction (MJ) formated during host cell invasion by apicomplexan parasites. As exemplified by Toxoplasma, the zoite loosely attaches to the target cell prior to invasion using a variety of cell surface adhesins (1). Subsequently, apical adhesion molecules such as AMA1and MIC2 are secreted from micronemes to the surface of zoite to initiate an intimate association between the apical end of the parasite and host cell (2). Invasion is initiated by formation of a moving junction (MJ) from proteins secreted from micronemes (AMA1) and the rhoptry neck (RON proteins) (2). At the same time, the contents of rhoptries (ROP) are secreted directly into the host cell, where they occupy small vesicular clusters. The parasite pushes itself through the MJ and enters into the parasitophorous vacuole (PV), which is formed by invagination of the host plasma membrane. The PV membrane (PVM) is extensively modified during invasion by secretion from rhoptries and exclusion of host proteins and (3). Lower image shows the detailed molecular interactions at the MJ. MIC proteins engage host cell surface receptors. The AMA1-RON2 interaction is thought to mediate formation of the junction. Adhesins such as MIC2 and AMA1 connect to the parasite cytoskeleton (actin, myosin, and the inner membrane complex (IMC)) through a bridging interaction with aldolase. Intramembrane proteases such as rhomboids (ROM) cleave adhesins within the membrane. Additional details are provided in the text. Areas of uncertainty or controversy are indicated by “?”.