CRMPA

CRMPA is a membrane-bound, GPCR-like apicomplexan protein that functions as an essential trigger for regulated rhoptry secretion during host cell invasion by Toxoplasma gondii (PMID:36245278). It assembles into a conserved apical complex (the CRMP complex) together with CRMPB, MIC15, and a thrombospondin type 1 domain-containing protein (TSP1); disruption of any of these components blocks rhoptry secretion and causes complete failure of host cell invasion (PMID:36602948). Rather than building the rhoptry secretion machinery itself, CRMPA and its partners only transiently associate with the exocytic site prior to invasion, and the presence of putative host cell-binding domains together with CRMPA's GPCR-like features indicates the complex acts as a host-molecular sensor that couples host cell contact to triggered rhoptry exocytosis (PMID:36245278). Beyond this sensing-and-triggering role, no direct ligand, downstream signaling partner, or structural model has been characterized in the available corpus.

1. 2022 High

   Established that TgCRMPs form a membrane-bound complex essential for rhoptry secretion, and distinguished them from structural machinery factors by showing they only transiently associate with the exocytic site — reframing them as a host-sensing trigger rather than part of the secretion apparatus.

   Evidence Tetrahymena-based transcriptomic screen, expansion microscopy, cryo-electron tomography, and loss-of-function analysis in Toxoplasma gondii

   PMID:36245278

   Open questions at the time

   • No host ligand or receptor for the putative host-binding domains identified
   • The signal-transduction mechanism linking CRMPA's GPCR-like features to exocytosis triggering is undefined
   • No structural model of the complex or its association with the exocytic site
2. 2023 High

   Defined the molecular composition of the CRMP complex — CRMPA, CRMPB, MIC15, and TSP1 — and demonstrated that disrupting the complex abolishes both rhoptry secretion and invasion, confirming its essential and non-redundant role.

   Evidence Co-immunoprecipitation/complex identification with conditional disruption of components and rhoptry secretion and invasion assays in T. gondii RH

   PMID:36602948

   Open questions at the time

   • Stoichiometry and spatial architecture of the four-subunit complex not resolved
   • Individual contributions of CRMPA versus its partners to host sensing not dissected
   • Whether the same complex composition holds across other strains or species not addressed

• The host molecular cue detected by the complex and the downstream signaling events that convert host contact into rhoptry exocytosis remain unidentified.
• No host ligand identified for the putative host cell-binding domains
• No signaling intermediates linking CRMPA to the exocytic machinery characterized
• No structural basis for complex assembly or exocytic-site recruitment