Aldolase Forms a Bridge between Cell Surface Adhesins and the Actin Cytoskeleton in Apicomplexan Parasites

Abstract

Host cell invasion by apicomplexan parasites requires coordinated interactions between cell surface adhesins and the parasite cytoskeleton. We have identified a complex of parasite proteins, including the actin binding protein aldolase, which specifically interacts with the C-terminal domains of several parasite adhesins belonging to the thrombospondin-related anonymous protein (TRAP) family. Binding of aldolase to the adhesin was disrupted by mutation of a critical tryptophan in the C domain, a residue that was previously shown to be essential for parasite motility. Our findings reveal a potential role for aldolase in connecting TRAP family adhesins with the cytoskeleton, and provide a model linking adhesion with motility in apicomplexan parasites.

The glideosome: a molecular machine powering motility and host-cell invasion by Apicomplexa

“…The integral membrane glycoprotein TgGAP50 functions as a receptor for TgMyoA-TgMLC in the IMC [24]. Confirmation of the immobilization of TgMyoA in the plane of the IMC is in good agreement with recent studies showing that the cytoplasmic tail of TgMIC2 and TRAP indirectly associate with actin via aldolase, a protein that binds filamentous actin (F-actin) [25,26]. Elucidation of the topology of the actomyosin system in the pellicle is crucial to our understanding of how force generated by the myosin motor can be transduced to the underlying cytoskeleton and hence can move the parasite body forward.…”

Molecular and functional aspects of parasite invasion

“…Gliding motility requires the coordinated interactions between cell-surface adhesins and the parasite cytoskeleton (Figure 2, movie 2). The identification of aldolase as an actin-binding protein has provided the first link between the actomyosin system and the adhesin molecules of the thrombospondin-related anonymous protein (TRAP) family both in Toxoplasma and Plasmodium [44,45]. These studies provide a generic model linking adhesion with motility in apicomplexan parasites.…”

“…The short cytoplasmic domains of TgMIC2 and TRAP are implicated in protein trafficking using a tyrosine-based motif [63,64]. The extreme C-terminus, which includes a conserved tryptophan residue, is involved in the interaction with aldolase, which exhibits a dual function as a glycolytic enzyme and an F-actin-binding protein [44,45].…”

Does protein phosphorylation govern host cell entry and egress by the Apicomplexa?

“…TgMIC2 is major determinant of gliding motility, connecting its cytoplasmic tail via TgALD to the actomyosin system (Brossier and David Sibley, 2005;Huynh and Carruthers, 2006;Jewett and Sibley, 2003). A phosphorylation site has been mapped in the highly acidic region of the TgMIC2 tail implicated in binding to TgALD; hence it is appealing to speculate that during invasion the phosphorylation of TgMIC2 might control the recruitment of the glycolytic enzyme in a timely, restricted fashion (Starnes et al, 2006) (Fig.…”