The Dynamic Roles of the Inner Membrane Complex in the Multiple Stages of the Malaria Parasite

Abstract

Apicomplexan parasites, such as human malaria parasites, have complex lifecycles encompassing multiple and diverse environmental niches. Invading, replicating, and escaping from different cell types, along with exploiting each intracellular niche, necessitate large and dynamic changes in parasite morphology and cellular architecture. The inner membrane complex (IMC) is a unique structural element that is intricately involved with these distinct morphological changes. The IMC is a double membrane organelle that forms de novo and is located beneath the plasma membrane of these single-celled organisms. In Plasmodium spp. parasites it has three major purposes: it confers stability and shape to the cell, functions as an important scaffolding compartment during the formation of daughter cells, and plays a major role in motility and invasion. Recent years have revealed greater insights into the architecture, protein composition and function of the IMC. Here, we discuss the multiple roles of the IMC in each parasite lifecycle stage as well as insights into its sub-compartmentalization, biogenesis, disassembly and regulation during stage conversion of P. falciparum.

Identification of novel inner membrane complex and apical annuli proteins of the malaria parasite Plasmodium falciparum

“…This is reflected in the architecture and proteome of the IMC. For apicomplexans, the IMC has three main functions: (a) it plays a major role in motility and invasion, (b) it confers stability and shape to the cell and (c) it provides a scaffolding framework during cytokinesis (Ferreira et al, 2021; Harding & Frischknecht, 2020). While the IMC of the motile stages serves as the anchor for proteins involved in gliding motility and host cell invasion (Baum, Gilberger, Frischknecht, & Meissner, 2008; Perrin et al, 2018; Soldati, Foth, & Cowman, 2004), the gametocyte IMC appears to serve a structural role (Dearnley et al, 2012; Parkyn Schneider et al, 2017; Sinden, 1982).…”

“…To date about 45 IMC proteins have been identified in Plasmodium (Ferreira et al, 2021), however, there is no comprehensive proteomic analysis of this structure available. From the confirmed IMC proteins it is evident that in addition to a common core set of conserved proteins found in all Alveolata, such as the Alveolins (Gould et al, 2011; Gould, Tham, Cowman, McFadden, & Waller, 2008), the IMC includes many lineage‐specific proteins, reflecting additional specialized roles (Kono et al, 2012).…”

Plasmodium falciparum PhIL1-associated complex plays an essential role in merozoite reorientation and invasion of host erythrocytes

“…an anchor for the motor complex, playing a significant role in gliding and thus invasion [5,15]. A number of studies have identified several proteins associated with the IMC and have provided insights into the organization and roles of the glideosome complex [5][6][7][16][17][18]. The basic motor complex in apicomplexan parasites that drives gliding motility and invasion is comprised of conserved components such as actin-MyoA-MTIP-GAP45-GAP40-GAP50--GAPMs-adhesin protein.…”

“…The IMC of an Apicomplexan parasite plays diverse roles in maintaining the structural stability of the zoite forms. It also acts as a scaffold for daughter cell development and plays a key role in motility and host-cell invasion [6,7]. Proteins involved in the organization of pellicle/IMC/glideosome include structural proteins such as alveolins (IMC1a-h), glideosome associated protein-40, -45, and -50 and glideosome associated proteins with multiple membrane spans (GAPMs), ISPs and these proteins together with MTIP (Myosin A tail domain interacting protein) anchor the actomyosin motor complex to the IMC [8,9].…”

“…Proteins involved in the organization of pellicle/IMC/glideosome include structural proteins such as alveolins (IMC1a-h), glideosome associated protein-40, -45, and -50 and glideosome associated proteins with multiple membrane spans (GAPMs), ISPs and these proteins together with MTIP (Myosin A tail domain interacting protein) anchor the actomyosin motor complex to the IMC [8,9]. These structures and proteins of glideosome/IMC are important as any disruption in the assembly of IMC blocks parasite invasion as well as sexual stage development [6,10].…”