PF3D7_1434400

PF3D7_1434400 (CLIP) is a component of a conserved apicomplexan microneme protein complex that couples parasite invasive machinery to host cell entry (PMID:37886905). In Toxoplasma gondii, the CLIP ortholog partners with CLAMP and SPATR to form a distinct microneme complex, and knockdown of complex members blocks rhoptry discharge without impairing parasite adhesion or microneme secretion, placing the complex specifically at the rhoptry-discharge step of invasion (PMID:37886905). In Plasmodium berghei, conditional deletion of clip impairs blood-stage growth and prevents merozoite invasion of erythrocytes, and in transmission stages abolishes sporozoite invasion of mosquito salivary glands and productive invasion of mammalian hepatocytes together with defects in cell traversal and gliding motility, phenocopying CLAMP-deficient parasites and establishing CLIP as essential for host cell invasion across invasive zoite stages (PMID:41929181). Beyond its membership in the CLAMP-CLIP-SPATR complex and these invasion phenotypes, no further mechanistic detail for PF3D7_1434400 itself has been characterized in the available corpus.

1. 2023 Medium

   Establishing whether CLIP belongs to a defined invasion complex and at which step it acts distinguished a general adhesion role from a specific rhoptry-discharge role.

   Evidence Co-immunoprecipitation, conditional knockdown, and rhoptry discharge/adhesion/secretion assays in Toxoplasma gondii tachyzoites, with phylogenetic analysis

   PMID:37886905

   Open questions at the time

   • CLIP function was tested in Toxoplasma, not directly in Plasmodium; the Plasmodium role was inferred only from conservation
   • The molecular mechanism by which the CLAMP-CLIP-SPATR complex enables rhoptry discharge is not defined
   • No structural model of the complex or of CLIP's contribution to it
2. 2026 Medium

   Direct loss-of-function of clip in Plasmodium tested whether the complex role is conserved and stage-specific, showing CLIP is required for invasion across the parasite life cycle rather than in a single stage.

   Evidence DiCre-based conditional clip deletion in P. berghei with erythrocyte invasion, salivary gland invasion, cell traversal, hepatocyte invasion, and gliding motility assays (preprint)

   PMID:41929181

   Open questions at the time

   • Not yet peer-reviewed; single-lab preprint
   • Does not resolve whether CLIP acts through the same rhoptry-discharge mechanism in Plasmodium as shown for the complex in Toxoplasma
   • The link between the gliding motility defect and the invasion/traversal defects is not mechanistically dissected

• How CLIP itself contributes biochemically to the CLAMP-CLIP-SPATR complex and to rhoptry discharge remains unresolved.
• No defined molecular activity for CLIP beyond complex membership
• No structural data on CLIP or its interface with CLAMP and SPATR
• Mechanistic basis of the gliding motility defect in CLIP-deficient sporozoites is unknown