CRMPB

CRMPB is a membrane-bound, apicomplexan-conserved protein of Toxoplasma gondii that functions within a multiprotein complex controlling rhoptry secretion and host cell invasion (PMID:36245278, PMID:36602948). Together with CRMPA, MIC15, and a thrombospondin type 1 domain-containing protein (TSP1), CRMPB forms the CRMP complex, whose disruption blocks rhoptry exocytosis and renders parasites unable to invade host cells (PMID:36602948). Rather than building the rhoptry secretion machinery itself, the CRMP complex transiently associates with the apical exocytic site prior to invasion, consistent with a role as a host-molecular sensor that couples host cell contact to rhoptry discharge (PMID:36245278). Beyond its membership in this complex and its requirement for triggering rhoptry secretion, no further biochemical or structural detail of CRMPB has been characterized in the available corpus.

1. 2022 High

   It was unknown whether an upstream factor distinct from the rhoptry secretion machinery couples host contact to exocytosis; this work established that membrane-bound TgCRMPs form a complex that transiently docks at the exocytic site and is required for rhoptry secretion and invasion without being needed to assemble the secretion apparatus.

   Evidence Tetrahymena-based transcriptomic screen, conditional knockdown/disruption, expansion microscopy, and cryo-electron tomography in Toxoplasma gondii

   PMID:36245278

   Open questions at the time

   • The molecular identity of the host signal or receptor sensed by the complex is undefined
   • How CRMPB is targeted to and transiently associates with the exocytic site is not resolved
   • The specific contribution of CRMPB versus other complex members is not dissected
2. 2023 High

   The precise composition of the invasion complex was undefined; reciprocal pulldowns established that CRMPB associates with CRMPA, MIC15, and TSP1, and that disrupting this complex specifically blocks rhoptry secretion and invasion, defining it as a conserved apicomplexan invasion complex.

   Evidence Co-immunoprecipitation/pulldown to define complex composition plus conditional disruption with rhoptry secretion and invasion assays in Toxoplasma gondii RH

   PMID:36602948

   Open questions at the time

   • The stoichiometry and structural architecture of the complex are unknown
   • The molecular mechanism by which complex integrity triggers rhoptry exocytosis is not established
   • Direct binding interfaces between CRMPB and each partner are not mapped

• The nature of the host molecular cue detected by the CRMP complex and the signaling steps linking that recognition to rhoptry discharge remain unknown.
• No host ligand or receptor for the putative sensor function has been identified
• The signal transduction pathway from host contact to exocytosis is uncharacterized