CEN1

PF3D7_0107000 (CEN1) is a calcium-binding EF-hand centrin that functions in Plasmodium falciparum cell division, localizing to the centriolar plaque during schizogony (PMID:18693242, PMID:37130129). It is expressed across multiple parasite life-cycle stages (sporozoites, asexual blood forms, gametocytes, oocysts) and associates with the parasite centrosome near the nucleus, and episomal expression rescues both a growth and a cytokinesis defect in a centrin-null Leishmania donovani line, establishing a conserved role in cell division (PMID:18693242). Within blood-stage schizonts CEN1 occupies the extranuclear (outer) compartment of the centriolar plaque and physically interacts with PfCen3 and the Sfi1-like centriolar plaque protein PfSlp (PF3D7_0710000), as shown by reciprocal co-immunoprecipitation and mass spectrometry (PMID:37130129). CEN1 undergoes reversible, Ca2+-dependent liquid-liquid phase separation in vitro that is dissolved by EDTA chelation and depends on its disordered N-terminus and EF-hand motifs, and it displays liquid-like dynamics at the centriolar plaque in live parasites, with condensate formation and dissolution timed to cell cycle progression (PMID:38150475). Beyond these findings, no further mechanistic detail on CEN1 has been characterized in the available corpus.

1. 2008 Medium

   Establishing whether the P. falciparum centrin CEN1 has a functional role in cell division rather than merely being a centrosome-associated protein, this work tied its centrosomal localization to a division phenotype.

   Evidence Immuno-EM and IFA co-staining with alpha-tubulin locating CEN1 to the centrosome, plus cross-species growth/cytokinesis complementation in centrin-KO Leishmania donovani

   PMID:18693242

   Open questions at the time

   • Complementation was done in a heterologous Leishmania system, not by loss-of-function in P. falciparum
   • Direct molecular partners at the centrosome were not identified
   • Stage-specific functional requirements were not dissected
2. 2023 Medium

   To define where CEN1 sits within the centriolar plaque and what it binds, this work resolved its extranuclear sub-compartment and identified its protein partners.

   Evidence Reciprocal anti-GFP co-immunoprecipitation of PfCen1-GFP with mass spectrometry and STED co-localization in P. falciparum 3D7 schizonts

   PMID:37130129

   Open questions at the time

   • Interaction stoichiometry and directness (direct vs. bridged) with PfCen3 and PfSlp not resolved
   • Functional consequence of the CEN1-PfSlp interaction not tested by perturbation
   • Single-lab episomal-tag data without endogenous validation
3. 2023 High

   To explain how CEN1 organizes at the centriolar plaque, this work showed it forms reversible calcium-dependent condensates, linking its EF-hand chemistry to a biophysical assembly mechanism.

   Evidence In vitro Ca2+-induced/EDTA-reversed LLPS of recombinant PfCen1-6His with N-terminus/EF-hand domain analysis, plus live-cell STED and inducible PfCen1-GFP overexpression time-lapse in P. falciparum 3D7

   PMID:38150475

   Open questions at the time

   • Whether LLPS is required for CEN1's division function in vivo was not tested by separation-of-function mutants
   • The physiological Ca2+ signal that triggers condensation at the plaque is not defined
   • How condensate dynamics couple mechanistically to spindle/centriolar plaque duplication is unresolved

• Whether CEN1 is essential in P. falciparum and how its Ca2+-dependent phase behavior mechanistically drives centriolar plaque duplication and schizont division remains unresolved.
• No direct loss-of-function/essentiality data for CEN1 in P. falciparum
• No structural model of the CEN1-PfCen3-PfSlp complex
• Causal link between LLPS and division phenotype untested