GAP70

GAP70 is a coccidian-specific paralog of the glideosome scaffolding protein GAP45 that spatially specializes the MyoA-glideosome in Toxoplasma gondii by recruiting myosin A to the apical cap of the parasite, a subcellular domain distinct from the broader pellicle recruitment mediated by GAP45 (PMID:20951968). Functional dissection established that whereas Plasmodium falciparum GAP45 can substitute for Toxoplasma GAP45, GAP70 confers apical-cap-restricted glideosome localization, marking it as a coccidian-tailored scaffolding component (PMID:20951968). Deletion genetics of glideosome components and analysis of compensatory relocalization between the MyoA- and MyoC-glideosomes corroborated GAP70's role as an apical-cap-restricted glideosome scaffold (PMID:25393004). Beyond this scaffolding/recruitment role at the apical cap, no further mechanistic detail has been characterized in the available corpus.

1. 2010 Medium

   It was unknown how glideosome recruitment could be spatially subdivided within the parasite pellicle; identifying GAP70 as a GAP45 paralog that recruits the MyoA-glideosome specifically to the apical cap established a mechanism for domain-specific motor positioning.

   Evidence Functional dissection with transgenera complementation, showing Plasmodium GAP45 could substitute for Toxoplasma GAP45 but GAP70 localized glideosome recruitment to the apical cap

   PMID:20951968

   Open questions at the time

   • Molecular basis of GAP70's apical-cap targeting was not defined
   • Direct biochemical interaction between GAP70 and MyoA was not resolved
   • Consequence for parasite motility and invasion not quantified in this study
2. 2014 Medium

   Whether GAP70 functions as a bona fide apical-cap-restricted scaffold, distinct from the MyoC-glideosome, was confirmed through deletion genetics and analysis of compensatory relocalization between the MyoA- and MyoC-glideosomes.

   Evidence Genetic and biochemical dissection of glideosome components, including deletion and analysis of compensatory relocalization between MyoA- and MyoC-glideosomes

   PMID:25393004

   Open questions at the time

   • Structural details of the GAP70 scaffold assembly not determined
   • Quantitative contribution of the apical-cap glideosome to invasion not isolated

• The molecular determinants of GAP70's apical-cap targeting and its direct binding partners within the MyoA-glideosome remain uncharacterized.
• No structural model of the GAP70 scaffold
• Recruitment mechanism to the apical cap unknown
• Direct MyoA-binding interface not mapped