Affinage · Plasmodium

Showing PF3D7_0702900 — CENTRIN is a alias.

PF3D7_0702900

centrin, putative

Audit flag: identity unverified
Annotated
2026-09-08
9 papers in source corpus 8 papers cited in narrative 8 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PF3D7_0702900 (centrin 2) is a Ca2+-binding EF-hand protein of the P. falciparum centriolar plaque (the parasite centrosome) that functions in the coordination of nuclear division and daughter-cell formation during schizogony (PMID:18693242, PMID:34535568). High-resolution and correlative imaging place it in the extranuclear compartment of the centriolar plaque, spatially distinct from the intranuclear microtubule-nucleating compartment and its spindle microtubules (PMID:34535568). Within this compartment it assembles through Ca2+-inducible liquid-liquid phase separation that depends on its disordered N-terminus and its Ca2+-binding EF-hand motifs; centrin condensates are dynamic and liquid-like in living parasites, and their concentration-dependent, regulated assembly and dissolution provide a mechanism for organizing the centriolar plaque (PMID:38150475). Beyond the centrosome, centrin 2 partially localizes to the posterior cup of the basal complex and is essential for parasite growth and replication, with its perturbation disrupting basal complex contraction and division synchrony; free intracellular calcium is necessary but not sufficient for this contraction (PMID:38829893). Centrin function connects to intranuclear tubulin homeostasis through its extranuclear interaction partner PfSlp, whose loss deregulates spindle microtubule abundance (PMID:37130129).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2008 Medium

    Establishing whether P. falciparum encodes centrins and whether they participate in cell division answered the basic question of centrin's existence and functional relevance in this parasite.

    Evidence Immunoelectron and immunofluorescence microscopy localizing centrin near the nucleus/centrosome, plus growth complementation of a centrin-KO Leishmania donovani line by an episomal PfCEN

    PMID:18693242

    Open questions at the time
    • Complementation in a heterologous system is an indirect proxy for the native P. falciparum role
    • Did not distinguish the four paralogs or assign function specifically to PF3D7_0702900
    • No direct loss-of-function in P. falciparum
  2. 2019 Medium

    Testing whether an alveolate-specific centrin is required for proliferation addressed whether centrin function is essential, revealing dispensability in a rodent-malaria ortholog.

    Evidence Live-cell GFP imaging, gene deletion with proliferation readout, and complex analysis of PbCEN-4 in P. berghei

    PMID:30541825

    Open questions at the time
    • Findings are for the P. berghei ortholog PbCEN-4, not PF3D7_0702900 itself
    • MTOC localization is 'putative'
    • Dispensability may not transfer to the P. falciparum paralog
  3. 2021 High

    Resolving where centrin sits within the centriolar plaque answered whether centrin nucleates spindle microtubules, showing it occupies a compartment separate from the intranuclear microtubule-organizing region.

    Evidence Super-resolution microscopy and correlative light/electron tomography of the P. falciparum centriolar plaque

    PMID:34535568

    Open questions at the time
    • Structural compartmentalization does not define centrin's molecular activity
    • Does not identify what recruits centrin to the extranuclear compartment
  4. 2022 High

    Mapping centrin within de novo basal bodies in microgametocytes addressed how the parasite builds its bipartite MTOC, placing centrin at the cytoplasmic basal body component that coordinates axoneme assembly with mitosis.

    Evidence Ultrastructure expansion microscopy (U-ExM/Pan-ExM) with 3D reconstruction, showing centrin/SAS6 enclosed by a SAS4-toroid in a SAS6/SAS4-dependent manner

    PMID:35077503

    Open questions at the time
    • Assembly context is gametocyte basal bodies, distinct from asexual centriolar plaque
    • Does not establish a functional requirement for centrin in basal body formation
  5. 2023 High

    Determining the biophysical basis of centriolar plaque assembly answered how centrin organizes at the centrosome, identifying Ca2+-inducible liquid-liquid phase separation driven by the disordered N-terminus and EF-hand motifs.

    Evidence In vitro LLPS reconstitution with N-terminus/EF-hand mutagenesis, live-cell STED, and inducible overexpression producing condensate-like assemblies in P. falciparum

    PMID:38150475

    Open questions at the time
    • Does not resolve which cellular Ca2+ signals trigger physiological condensation
    • Co-condensation partners among centrins not fully mapped for PF3D7_0702900 specifically
  6. 2023 Medium

    Identifying a centrin-interacting Sfi1-like protein connected the extranuclear centrin compartment to intranuclear tubulin homeostasis, showing this compartment regulates spindle microtubule abundance.

    Evidence Co-immunoprecipitation identifying PfSlp, plus conditional PfSlp knockdown causing excess microtubules and aberrant spindles in P. falciparum

    PMID:37130129

    Open questions at the time
    • Phenotypes derive from PfSlp knockdown, not direct centrin manipulation
    • Mechanism by which the extranuclear compartment controls intranuclear tubulin is unresolved
  7. 2024 Medium

    Direct loss-of-function of PF3D7_0702900 answered whether it is essential and where else it acts, establishing an additional basal complex localization and a role in contraction and division synchrony.

    Evidence U-ExM localization, live-cell microscopy, conditional knockdown, and calcium manipulation in P. falciparum

    PMID:38829893

    Open questions at the time
    • Basal complex contraction defects were variable
    • Molecular mechanism linking centrin to contraction is not defined
    • How its centrosomal versus basal complex functions are partitioned is unclear
  8. 2020 Low

    Observing abnormal centrin distribution upon PfMCMBP depletion indicated that centrin positioning depends on the integrity of nuclear division regulators.

    Evidence Conditional depletion of PfMCMBP with immunofluorescence readout of centrin in P. falciparum

    PMID:33124706

    Open questions at the time
    • Ancillary readout in a study of a different protein, not direct centrin manipulation
    • Single observation without orthogonal confirmation
    • No mechanistic link between PfMCMBP and centrin established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular activity of centrin 2 at the basal complex and how its Ca2+-responsive condensation is translated into force generation or contraction remain open.
  • No defined molecular effector coupling centrin to basal complex contraction
  • How Ca2+ signals are timed relative to condensation in vivo is unknown
  • Functional distinction among the four PfCEN paralogs at each site not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
OTHER P. FALCIPARUM CENTRINS (CO-CONDENSATION)PFSLP (SFI1-LIKE CENTRIOLAR PLAQUE PROTEIN)
Complex memberships
Basal body (centrin/SAS6 core enclosed by SAS4-toroid, in gametocytes)Centriolar plaque (extranuclear compartment)Multi-centrin complex (P. berghei PbCEN-4)

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 P. falciparum possesses four centrin paralogs (PfCENs) with four Ca2+-binding EF-hand domains; immunoelectron microscopy showed centrin protein is expressed in close proximity to the nucleus of sporozoites and asexual schizonts, and confocal/widefield microscopy with double-staining (anti-α-tubulin and anti-centrin) indicated association with the parasite centrosome. Episomal expression of PfCENs in a centrin-knockout Leishmania donovani line (growth complementation assay) showed that one PfCEN partially restored growth rate and overcame a cytokinesis defect, providing evidence for centrin involvement in cell division. Immunoelectron microscopy, immunofluorescence microscopy (double-staining with α-tubulin), growth complementation in centrin-KO Leishmania donovani, real-time PCR The Journal of biological chemistry Medium 18693242
2021 Super-resolution and correlative light/electron tomography revealed that centrin is confined to the extranuclear compartment of the centriolar plaque (the centrosome of P. falciparum), while microtubules are nucleated in a separate, previously unknown extended intranuclear, chromatin-free, protein-dense compartment. This established two distinct spatial compartments of the centriolar plaque and showed centrin does not co-localize with intranuclear spindle microtubules. Super-resolution microscopy (STED/SIM), time-lapse imaging, correlative light and electron tomography Life science alliance High 34535568
2019 In P. berghei, a centrin (PbCEN-4, an alveolate-specific centrin orthologous to one of the PfCENs) localizes to the putative MTOC during asexual replicative stages as shown by live-cell imaging, forms a multi-protein complex with other centrins, but is dispensable for parasite proliferation (gene deletion had no detectable growth defect). Live-cell imaging (GFP-tagging), gene deletion (knockout), co-immunoprecipitation/complex analysis Biology open Medium 30541825
2022 In P. berghei microgametocytes, centrin (along with γ-tubulin, SAS4, and SAS6) forms distinct subdomains within de novo assembled basal bodies in a SAS6- and SAS4-dependent manner from a deuterosome-like structure. Ultrastructure expansion microscopy (U-ExM/Pan-ExM) revealed centrin and SAS6 are surrounded by a SAS4-toroid in the lumen of the microtubule wall at basal bodies, placing centrin at the cytoplasmic basal body component of the bipartite MTOC that coordinates axoneme assembly with mitosis. Ultrastructure expansion microscopy (U-ExM, Pan-ExM), 3D reconstruction, immunofluorescence PLoS pathogens High 35077503
2023 Multiple P. falciparum centrins (including those at the centriolar plaque) undergo Ca2+-inducible liquid-liquid phase separation (LLPS) in vitro. The disordered N-terminus and Ca2+-binding EF-hand motifs are essential features for reversible biomolecular condensation. Certain centrins form co-condensates with each other. In vivo, live-cell STED microscopy revealed liquid-like dynamics of centrosomal centrin, and an inducible overexpression system showed concentration-dependent formation of extra-centrosomal centrin assemblies with condensate-like properties; timing of foci formation/dissolution suggests regulated assembly. In vitro LLPS assay, mutagenesis (N-terminus deletion, EF-hand mutations), live-cell STED microscopy, inducible protein overexpression system PLoS pathogens High 38150475
2023 A novel Sfi1-like centriolar plaque protein (PfSlp) was identified as a centrin-interacting protein residing in the extranuclear compartment of the centriolar plaque; conditional knockdown of PfSlp caused growth delay and reduced daughter cell number, increased intranuclear tubulin abundance, and produced excess microtubules and aberrant mitotic spindles—establishing a functional link between the extranuclear centrin-containing compartment and intranuclear tubulin homeostasis. Co-immunoprecipitation/protein interaction assay, conditional knockdown, immunofluorescence microscopy, time-lapse microscopy PLoS pathogens Medium 37130129
2024 EF-hand-containing P. falciparum Centrin 2 (PF3D7_0702900) partially localizes to the posterior cup subcompartment of the basal complex (in addition to its centrosomal localization), is essential for parasite growth and replication, and its perturbation causes variable defects in basal complex contraction and synchrony. Free intracellular calcium was shown to be necessary but not sufficient for basal complex contraction. Ultrastructure expansion microscopy (U-ExM), live-cell microscopy, conditional knockdown/loss-of-function, calcium manipulation assays PLoS pathogens Medium 38829893
2020 Depletion of PfMCMBP in P. falciparum led to abnormal centrin distribution (by immunofluorescence) alongside aberrant mitotic spindle formation, demonstrating that centrin localization at the centriolar plaque is sensitive to disruption of nuclear division regulators. (Note: this is an indirect observation of centrin behavior consequent to PfMCMBP depletion, not a direct manipulation of centrin.) Conditional depletion (PfMCMBP), immunofluorescence microscopy Cellular microbiology Low 33124706

Source papers

Stage 0 corpus · 9 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Centrins, cell cycle regulation proteins in human malaria parasite Plasmodium falciparum. The Journal of biological chemistry 67 18693242
2021 An extended DNA-free intranuclear compartment organizes centrosome microtubules in malaria parasites. Life science alliance 56 34535568
2022 Expansion microscopy of Plasmodium gametocytes reveals the molecular architecture of a bipartite microtubule organisation centre coordinating mitosis with axoneme assembly. PLoS pathogens 52 35077503
2019 Plasmodium centrin PbCEN-4 localizes to the putative MTOC and is dispensable for malaria parasite proliferation. Biology open 24 30541825
2020 Plasmodium berghei Kinesin-5 Associates With the Spindle Apparatus During Cell Division and Is Important for Efficient Production of Infectious Sporozoites. Frontiers in cellular and infection microbiology 18 33154955
2020 Depletion of the mini-chromosome maintenance complex binding protein allows the progression of cytokinesis despite abnormal karyokinesis during the asexual development of Plasmodium falciparum. Cellular microbiology 15 33124706
2023 Malaria parasite centrins can assemble by Ca2+-inducible condensation. PLoS pathogens 11 38150475
2023 An Sfi1-like centrin-interacting centriolar plaque protein affects nuclear microtubule homeostasis. PLoS pathogens 7 37130129
2024 Elucidating the spatio-temporal dynamics of the Plasmodium falciparum basal complex. PLoS pathogens 3 38829893