Dual acylation of the 45kDa gliding-associated protein (GAP45) in Plasmodium falciparum merozoites

Rees-Channer, Roxanne R.; Martin, Stephen R.; Green, Judith L.; Bowyer, Paul W.; Grainger, Munira; Molloy, Justin E.; Holder, Anthony A.

doi:10.1016/j.molbiopara.2006.04.008

Cited by 95 publications

(130 citation statements)

References 20 publications

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“…Like wild-type GAP45, however, GAP45-YFP is also associated with the membrane of the IMC due to Nterminal palmitoylation and myristoylation of the protein (Johnson, DeVore, and Beckers, unpublished data). A similar modification has also been described for the protein found in Plasmodium (Rees-Channer et al, 2006). FRAP analysis on TgGAP45-YFP demonstrates that the protein is able to diffuse freely along the IMC ( Figure 2A).…”

Section: Tggap50 Is Immobilized In the Inner Membrane Complex Of Toxosupporting

confidence: 73%

Immobilization of the Type XIV Myosin Complex inToxoplasma gondii

Johnson

Rajfur

Jacobson

et al. 2007

MBoC

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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.

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Section: Tggap50 Is Immobilized In the Inner Membrane Complex Of Toxosupporting

confidence: 73%

Immobilization of the Type XIV Myosin Complex inToxoplasma gondii

Johnson

Rajfur

Jacobson

et al. 2007

MBoC

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“…It is possible that the binding interface involves more than the 5 amino acids of the cytoplasmic domain of PfGAP50 or that additional proteins are required for complex stability. Indeed, it has been reported that PfGAP45 is both myristoylated and palmitoylated (35). This may facilitate penetration of PfGAP45 into the bilayer, providing a larger interaction area.…”

Section: Discussionmentioning

confidence: 99%

Tracking Glideosome-Associated Protein 50 Reveals the Development and Organization of the Inner Membrane Complex of Plasmodium falciparum

et al. 2011

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The most deadly of the human malaria parasites, Plasmodium falciparum, has different stages specialized for invasion of hepatocytes, erythrocytes, and the mosquito gut wall. In each case, host cell invasion is powered by an actin-myosin motor complex that is linked to an inner membrane complex (IMC) via a membrane anchor called the glideosome-associated protein 50 (PfGAP50). We generated P. falciparum transfectants expressing green fluorescent protein (GFP) chimeras of PfGAP50 (PfGAP50-GFP). Using immunoprecipitation and fluorescence photobleaching, we show that C-terminally tagged PfGAP50-GFP can form a complex with endogenous copies of the linker protein PfGAP45 and the myosin A tail domain-interacting protein (MTIP). Full-length PfGAP50-GFP is located in the endoplasmic reticulum in early-stage parasites and then redistributes to apical caps during the formation of daughter merozoites. In the final stage of schizogony, the PfGAP50-GFP profile extends further around the merozoite surface. Three-dimensional (3D) structured illumination microscopy reveals the early-stage IMC as a doubly punctured flat ellipsoid that separates to form claw-shaped apposed structures. A GFP fusion of PfGAP50 lacking the C-terminal membrane anchor is misdirected to the parasitophorous vacuole. Replacement of the acid phosphatase homology domain of PfGAP50 with GFP appears to allow correct trafficking of the chimera but confers a growth disadvantage.

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“…Furthermore, a large num-ber of substrates have been predicted based on bioinformatics searches and identified in a palmitome analysis of P. falciparum (9,10). Additionally, palmitoylation of several apicomplexan proteins has been experimentally proven to be critical for correct protein localization and function (11)(12)(13)(14)(15). The fast reaction kinetics of palmitoylation (16) and the reversibility of this modification contribute to its effectiveness as a regulatory system for protein dynamics.…”

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confidence: 99%

Characterization of a Serine Hydrolase Targeted by Acyl-protein Thioesterase Inhibitors in Toxoplasma gondii

Kemp

Rusch²,

Adibekian

et al. 2013

Journal of Biological Chemistry

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Background: S-Palmitoylation is an important reversible modification that involves the action of an acyl-protein thioesterase (APT). Results:We identified an active serine hydrolase (TgASH1) specifically targeted by human APT1 inhibitors in Toxoplasma gondii. Conclusion: TgASH1 is dispensable and cannot be solely responsible for S-depalmitoylation in Apicomplexa. Significance: ␤-Lactone-based APT1 inhibitors hit multiple targets in T. gondii and severely compromise parasite survival.

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Dual acylation of the 45kDa gliding-associated protein (GAP45) in Plasmodium falciparum merozoites

Cited by 95 publications

References 20 publications

Immobilization of the Type XIV Myosin Complex inToxoplasma gondii

Immobilization of the Type XIV Myosin Complex inToxoplasma gondii

Tracking Glideosome-Associated Protein 50 Reveals the Development and Organization of the Inner Membrane Complex of Plasmodium falciparum

Characterization of a Serine Hydrolase Targeted by Acyl-protein Thioesterase Inhibitors in Toxoplasma gondii

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