Immobilization of the Type XIV Myosin Complex inToxoplasma gondii

Abstract

The substrate-dependent movement of apicomplexan parasites such as Toxoplasma gondii and Plasmodium sp. is driven by the interaction of a type XIV myosin with F-actin. A complex containing the myosin-A heavy chain, a myosin light chain, and the accessory protein GAP45 is attached to the membranes of the inner membrane complex (IMC) through its tight interaction with the integral membrane glycoprotein GAP50. For the interaction of this complex with F-actin to result in net parasite movement, it is necessary that the myosin be immobilized with respect to the parasite and the actin with respect to the substrate the parasite is moving on. We report here that the myosin motor complex of Toxoplasma is firmly immobilized in the plane of the IMC. This does not seem to be accomplished by direct interactions with cytoskeletal elements. Immobilization of the motor complex, however, does seem to require cholesterol. Both the motor complex and the cholesterol are found in detergent-resistant membrane domains that encompass a large fraction of the inner membrane complex surface. The observation that the myosin XIV motor complex of Toxoplasma is immobilized within this cholesterol-rich membrane likely extends to closely related pathogens such as Plasmodium and possibly to other eukaryotes.

Subcellular localization and dynamics of a digalactolipid-like epitope in Toxoplasma gondii

“…5A), our study suggests that during invasion DGLE might be associated with actin and/or micronemal proteins. Alternatively, Johnson et al (64) recently showed that GAP50 and the myosin complex are immobilized within the inner membrane complex at the level of DRM domains, which are enriched in sterols and have a higher density than DRMs classically reported in eukaryotic cells. DGLE might be a component of such inner membrane complex DRMs.…”

Origin, composition, organization and function of the inner membrane complex of Plasmodium falciparum gametocytes

“…The glideosome proteins include myosin-A (MyoA), myosin-A tail domain interacting protein (MTIP) (Bergman et al, 2003;Herm-Götz et al, 2002) and the glideosome-associated proteins 45 and 50 (GAP45 and GAP50) (Gaskins et al, 2004). P. falciparum GAP50 is an integral membrane protein that anchors pre-complexed GAP45-MTIP-MyoA (Johnson et al, 2007). Host cell invasion is thought to require binding of the actinmyosin complex to adhesive proteins such as the merozoite thrombospondin-related adhesive protein (mTRAP).…”

GAP45 Phosphorylation Controls Assembly of the Toxoplasma Myosin XIV Complex

“…These parasites lack structures commonly used by other cells for motility (e.g., pseudopods, cilia, and flagella), instead relying on a unique, substrate-dependent mechanism termed gliding motility (1). This complex process involves not only an actin-myosin motor but also proteins that connect the F-actin to extracellular ligands and that anchor the myosin motor in the inner membrane complex (9,15). The motility of Toxoplasma tachyzoites is activated by the decrease in potassium concentration in their immediate environment that follows disruption of an infected host cell (20).…”

“…MyoA is found in a complex with an atypical myosin light chain (MLC1) and two novel proteins, GAP50 and GAP45 (9). GAP50 is an integral membrane protein of the inner membrane complex (IMC) that anchors and immobilizes the motor complex in the plane of the IMC membrane in a cholesterol-dependent manner (15). The function of the fourth subunit of the motor complex, GAP45, is less clear.…”