Affinage

CCDC61

Centrosomal protein CCDC61 · UniProt Q9Y6R9

Length
512 aa
Mass
57.4 kDa
Annotated
2026-06-09
13 papers in source corpus 9 papers cited in narrative 9 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCDC61 (hVFL3) is a centriolar/centrosomal structural protein that organizes the geometry and connectivity of basal bodies and centrioles across eukaryotes (PMID:31789463, PMID:32375023, PMID:6699086). Crystal structures establish it as a structural paralog of SAS6: it retains two homodimerization interfaces homologous to those of SAL6 but uses them to polymerize into linear filaments rather than rings, and it directly binds microtubules through residues required for ciliary function (PMID:32375023). In human cells it localizes to subdistal appendages and proximal ends of the mother centriole, where it directly binds microtubules, physically interacts with Cep170, and is required for centrosome cohesion and interphase centrosome positioning; loss of CCDC61 increases mother-daughter centriole distance and exacerbates splitting when the rootletin/C-Nap1 linker is disrupted (PMID:31789463). The Cep170 interaction supports the Cep170-TBK1 association required for microtubule stability, and CCDC61 depletion disrupts intrinsic spindle symmetry and mitotic spindle assembly (PMID:30354798). Across unicellular eukaryotes and Xenopus, its orthologs localize at the junction between basal bodies and striated rootlets and are required for basal body rotational asymmetry, docking, spacing and polarization, templated centriole duplication, and mechanical coupling that synchronizes flagellar beating (PMID:35067717, PMID:28367320, PMID:26684142, PMID:11267867, PMID:6699086). Its centrosome-specific binding is sufficiently selective that a CCDC61-derived peptide captures intact centrosomes for proteome isolation (PMID:37852252).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1984 Medium

    Established the founding phenotype linking this gene to ciliary architecture by asking whether basal body orientation depends on associated fibers rather than on beating machinery.

    Evidence High-speed cinephotomicrography and polarity marker analysis of the Chlamydomonas vfl-3 mutant lacking striated fibers and microtubular rootlets

    PMID:6699086

    Open questions at the time
    • Gene product not molecularly identified
    • Mechanism connecting fibers to rotational orientation unknown
  2. 2001 Medium

    Defined a specific requirement in centriole biogenesis by distinguishing templated from de novo assembly pathways.

    Evidence Genetic analysis of vfl3 mutant with quantification of de novo vs templated centriole assembly in centrioleless Chlamydomonas

    PMID:11267867

    Open questions at the time
    • Molecular role in templating unresolved
    • No biochemical activity assigned
  3. 2015 Medium

    Showed how the structures depending on this gene contribute to organismal function by testing whether flagellar synchronization is mechanical or hydrodynamic.

    Evidence Controlled external-flow hydrodynamics and high-speed imaging of vfl3 mutant Chlamydomonas flagella

    PMID:26684142

    Open questions at the time
    • Uses mutant as a tool; does not define the protein's molecular function
    • Coupling structure not molecularly dissected
  4. 2017 Medium

    Connected the ortholog to a molecular recruitment event and basal body asymmetry, advancing from phenotype to a defined molecular dependency.

    Evidence RNAi depletion, immunofluorescence localization, and basal body/rootlet phenotyping in Paramecium tetraurelia

    PMID:28367320

    Open questions at the time
    • Direct interaction with Centrin 3 not demonstrated
    • Mechanism of asymmetry specification unknown
  5. 2018 Medium

    Extended function into mitosis and into a defined human protein interaction, asking how CCDC61 contributes to spindle symmetry and microtubule stability.

    Evidence siRNA knockdown, microtubule tip-tracking, and co-immunoprecipitation in human cells

    PMID:30354798

    Open questions at the time
    • Whether CCDC61 directly bridges Cep170-TBK1 vs indirectly is unresolved
    • Structural basis of spindle symmetry effect unknown
  6. 2019 High

    Defined the human protein's centriolar localization and a coherent set of structural roles, establishing it as a centrosome cohesion and positioning factor that binds microtubules and Cep170.

    Evidence Immunofluorescence, co-IP, microtubule co-sedimentation, and siRNA epistasis with the C-Nap1 linker in human cells

    PMID:31789463

    Open questions at the time
    • Mechanism by which it enforces cohesion at the linker not detailed
    • Spatial relationship to subdistal appendage assembly unresolved
  7. 2020 High

    Provided the structural mechanism by revealing CCDC61 as a SAS6 paralog that polymerizes into filaments and directly binds microtubules via residues required for ciliary function.

    Evidence X-ray crystallography, in vitro microtubule-binding assay, and mutagenesis with Chlamydomonas ciliary complementation

    PMID:32375023

    Open questions at the time
    • In vivo architecture of the filaments not visualized
    • How filament assembly couples to centriole/rootlet positioning unknown
  8. 2022 Medium

    Established the vertebrate multiciliated-cell role, showing CCDC61 is required for basal body docking, spacing, polarization, and cilia-driven fluid flow.

    Evidence Morpholino knockdown, immunofluorescence localization, and fluid-flow assay in Xenopus ciliated epidermis

    PMID:35067717

    Open questions at the time
    • Molecular partners in vertebrate basal body/rootlet junction not identified
    • Relationship to apical cytoskeleton mechanistically undefined
  9. 2023 Medium

    Demonstrated the selectivity of CCDC61's centrosome binding by turning it into a one-step centrosome capture reagent.

    Evidence Affinity capture with a CCDC61-derived peptide, mass spectrometry, and electron microscopy verification of intact centrosomes

    PMID:37852252

    Open questions at the time
    • Endogenous binding partner of the capture peptide not defined
    • Does not address native CCDC61 function

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CCDC61 filament assembly is spatially regulated to coordinate subdistal appendage organization, centriole cohesion, and rootlet anchoring within a single mechanistic framework remains open.
  • No in vivo structure of CCDC61 filaments at the centriole
  • Regulatory inputs governing its assembly/disassembly unknown
  • Direct vs indirect contribution to Cep170-TBK1 microtubule stability unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2 GO:0005198 structural molecule activity 1
Localization
GO:0005815 microtubule organizing center 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-1640170 Cell Cycle 1
Partners
CEP170TBK1

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 Ccdc61 localizes to centrosomes and is required for spindle assembly and symmetry in mitosis; its depletion causes loss of intrinsic symmetry of microtubule tracks within the spindle and impairs the binding between Cep170 and TANK-binding kinase 1 (TBK1), an interaction required for microtubule stability. siRNA knockdown, microtubule tip-tracking experiments, co-immunoprecipitation, fluorescence microscopy Molecular biology of the cell Medium 30354798
2019 hVFL3/CCDC61 localizes to subdistal appendages (SAP) and proximal ends of the mother centriole, physically interacts with Cep170, is required for centrosome cohesion (depletion increases mother-daughter centriole distance and exacerbates centriole splitting when the rootletin/C-Nap1 linker is disrupted), is required for centrosome positioning in interphase cells, and directly binds microtubules. Immunofluorescence, co-immunoprecipitation (physical interaction with Cep170), siRNA depletion with phenotypic rescue, microtubule co-sedimentation assay Biology of the cell High 31789463
2020 CCDC61 is a structural paralog of SAS6; crystal structures reveal it contains two homodimerization interfaces homologous to SAS6 but that drive formation of linear filaments rather than rings. CCDC61 binds microtubules, and residues involved in microtubule binding are required for ciliary function in Chlamydomonas. X-ray crystallography, in vitro microtubule-binding assay, mutagenesis of microtubule-binding residues, Chlamydomonas complementation/ciliary function assay Structure High 32375023
2022 Ccdc61 encodes a basal body component localizing proximally at the junction with striated rootlets in Xenopus multiciliated cells; morpholino knockdown causes defects in basal body docking, spacing, and polarization, impairs the apical cytoskeleton, and reduces ciliary beating and cilia-powered fluid flow. Morpholino knockdown in Xenopus embryonic ciliated epidermis, immunofluorescence localization, fluid-flow assay Journal of cell science Medium 35067717
2023 A synthetic peptide derived from the CCDC61 protein specifically captures intact centrosomes via affinity pull-down, enabling centrosome proteome isolation (CAPture-MS), demonstrating that CCDC61 provides a centrosome-specific molecular handle sufficient for one-step centrosome purification. Affinity capture using CCDC61-derived peptide coupled to beads, mass spectrometry, electron microscopy verification of intact centrosomes Developmental cell Medium 37852252
2017 In Paramecium tetraurelia, VFL3-A (ortholog of CCDC61/VFL3) localizes transiently near basal bodies at early duplication, at the junction between the striated rootlet and the basal body, is required for recruitment of Centrin 3, and is required for rotational asymmetry of the basal body that specifies assembly sites for appendages guiding basal body movement to the cell surface; depletion results in unanchored basal bodies with disorganized rootlet distribution. RNAi depletion in Paramecium, immunofluorescence localization, phenotypic analysis of basal body docking and rootlet organization Cilia Medium 28367320
2015 Using the vfl3 mutant of Chlamydomonas (which lacks normal striated fibers connecting flagella), hydrodynamic synchronization experiments demonstrated that flagellar synchronization requires intracellular mechanical coupling through internal fibers rather than hydrodynamic forces; vfl3 cells with impaired mechanical connections between flagella cannot synchronize under physiological hydrodynamic forces. Controlled external flow hydrodynamics experiments, high-speed imaging of vfl3 mutant flagella Physical review letters Medium 26684142
2001 In Chlamydomonas, a mutation in the VFL3 gene abolishes the templated centriole duplication pathway without eliminating de novo centriole assembly, establishing that VFL3 is specifically required for the templated (preexisting-centriole-dependent) pathway of centriole duplication. Genetic analysis of vfl3 mutant, quantification of de novo vs templated centriole assembly in centrioleless cells Current biology : CB Medium 11267867
1984 In Chlamydomonas vfl-3 mutant, which lacks normal striated fibers and microtubular rootlets, flagella beat vigorously but display variable rotational orientation of basal bodies, establishing that striated fibers and/or associated structures are required for establishing or maintaining correct rotational orientation of basal bodies rather than for flagellar beating per se. High-speed cinephotomicrography, structural polarity marker analysis in vfl-3 mutant The Journal of cell biology Medium 6699086

Source papers

Stage 0 corpus · 13 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Kinetics and regulation of de novo centriole assembly. Implications for the mechanism of centriole duplication. Current biology : CB 112 11267867
1989 Nucleus-basal body connector in Chlamydomonas: evidence for a role in basal body segregation and against essential roles in mitosis or in determining cell polarity. Cell motility and the cytoskeleton 59 2696598
2015 Hydrodynamics Versus Intracellular Coupling in the Synchronization of Eukaryotic Flagella. Physical review letters 50 26684142
1984 Flagellar waveform and rotational orientation in a Chlamydomonas mutant lacking normal striated fibers. The Journal of cell biology 32 6699086
2017 Basal body positioning and anchoring in the multiciliated cell Paramecium tetraurelia: roles of OFD1 and VFL3. Cilia 24 28367320
2018 Ccdc61 controls centrosomal localization of Cep170 and is required for spindle assembly and symmetry. Molecular biology of the cell 21 30354798
2019 Emergence of a Bilaterally Symmetric Pattern from Chiral Components in the Planarian Epidermis. Developmental cell 20 31743665
2023 Proteomic profiling of centrosomes across multiple mammalian cell and tissue types by an affinity capture method. Developmental cell 18 37852252
2013 Katanin localization requires triplet microtubules in Chlamydomonas reinhardtii. PloS one 15 23320108
2019 hVFL3/CCDC61 is a component of mother centriole subdistal appendages required for centrosome cohesion and positioning. Biology of the cell 13 31789463
2020 CCDC61/VFL3 Is a Paralog of SAS6 and Promotes Ciliary Functions. Structure (London, England : 1993) 10 32375023
2022 Lrrcc1 and Ccdc61 are conserved effectors of multiciliated cell function. Journal of cell science 9 35067717
2020 Genetic basis of relapsing polychondritis revealed by family-based whole-exome sequencing. International journal of rheumatic diseases 2 32107856

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