Affinage

LRRCC1

Leucine-rich repeat and coiled-coil domain-containing protein 1 · UniProt Q9C099

Length
1032 aa
Mass
119.6 kDa
Annotated
2026-06-10
22 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

LRRCC1 (CLERC/VFL1) is a conserved leucine-rich repeat and coiled-coil protein that organizes the distal region of centrioles and basal bodies to control their number, orientation, and competence for ciliogenesis (PMID:11285274, PMID:35319462). It localizes asymmetrically to two consecutive triplet microtubules in the distal lumen of human centrioles, forming part of a rotationally asymmetric 'acorn' structure, a positioning anticipated by the original Chlamydomonas work showing Vfl1p inside the basal body lumen at the distal end in a rotationally asymmetric pattern (PMID:11285274, PMID:35319462). Within this distal module LRRCC1 acts downstream of C2CD3 and SSNA1 in a hierarchical targeting axis and contributes to recruiting C2CD3, linking it to a defined molecular pathway for distal centriole organization (PMID:35319462). Functionally, LRRCC1 maintains centrosome structural integrity through mitosis—its depletion causes centrosome splitting and multipolar spindles (PMID:18728398)—and supports ciliary assembly and signaling, with loss producing defects in centriole structure and primary ciliogenesis (PMID:35319462). In multiciliated cells it localizes proximally at the junction with striated rootlets and is required for basal body docking, spacing, and polarization and for normal ciliary beating and fluid flow (PMID:35067717). The conserved requirement for the gene in establishing basal body number, positioning, and flagellar apparatus integrity was first defined genetically in Chlamydomonas vfl-1 mutants (PMID:3972905). The biochemical activity of the leucine-rich repeat and coiled-coil domains has not been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1985 Medium

    Established that the gene controls basal body number, positioning, and flagellar apparatus integrity, defining the core biological problem before any molecular identity was known.

    Evidence Genetic mapping and light/electron microscopy of Chlamydomonas vfl-1 mutants

    PMID:3972905

    Open questions at the time
    • No molecular identity or protein product defined
    • Mechanism linking the gene to basal body positioning unknown
  2. 1989 Low

    Distinguished VFL1 function from the centrin/nucleus-basal body connector pathway, showing it acts in a separate route to basal body number and positioning.

    Evidence Anti-centrin immunofluorescence comparing vfl-1 and vfl-2 mutants

    PMID:2696598

    Open questions at the time
    • Single comparative immunofluorescence result
    • Does not identify the alternative pathway VFL1 operates in
  3. 2001 High

    Identified the molecular product as a leucine-rich repeat/coiled-coil protein and localized it asymmetrically inside the distal basal body lumen, making it the first molecular marker of basal body rotational asymmetry.

    Evidence Tagged-allele cloning, complementation rescue, basal body co-purification, immunogold EM in Chlamydomonas

    PMID:11285274

    Open questions at the time
    • No molecular partners identified
    • Biochemical activity of the domains undefined
    • Mechanism by which it imposes rotational asymmetry unknown
  4. 2008 Medium

    Extended the function to human cells, showing the centrosomal ortholog maintains centrosome structural integrity required for mitotic spindle bipolarity.

    Evidence Immunofluorescence and RNAi depletion with spindle and centriole counting readouts in human cells

    PMID:18728398

    Open questions at the time
    • Single lab
    • Molecular basis of centrosome cohesion role not defined
    • No interaction partners identified
  5. 2013 Low

    Linked vfl1 to basal body structural integrity through shared microtubule-drug sensitivity with other basal body assembly mutants.

    Evidence Taxol sensitivity and double-mutant analysis in Chlamydomonas

    PMID:23320108

    Open questions at the time
    • Pharmacological inference only, no direct structural mechanism
    • vfl1 one of several mutants tested
  6. 2019 Medium

    Showed the gene is required for centriole appendages that tether cytoskeletal connectors, aligning centrioles along polarity fields during tissue patterning.

    Evidence RNAi knockdown in planaria with centriole positioning and polarity readouts

    PMID:31743665

    Open questions at the time
    • Molecular composition of the appendages unknown
    • Direct binding partners not identified
  7. 2022 High

    Resolved the precise structural position of human LRRCC1 to two consecutive distal-lumen triplet microtubules and placed it functionally with C2CD3 in an 'acorn' module driving distal centriole organization and primary ciliogenesis.

    Evidence U-ExM super-resolution imaging, co-localization, and siRNA depletion with ciliary assembly and signaling readouts in human cells

    PMID:35319462

    Open questions at the time
    • Direct physical interaction with C2CD3 not demonstrated biochemically
    • Mechanism of triplet-microtubule selectivity unknown
  8. 2022 High

    Demonstrated a tissue-level role in multiciliated cells, where the protein localizes near striated rootlets and is required for basal body docking, polarization, and cilia-driven fluid flow.

    Evidence Morpholino knockdown, immunofluorescence, high-speed video and fluid flow assays in Xenopus ciliated epidermis

    PMID:35067717

    Open questions at the time
    • Proximal rootlet-junction localization differs from distal-lumen localization in human centrioles; relationship not reconciled
    • Direct rootlet-connecting partners not identified
  9. 2025 Medium

    Defined a hierarchical targeting axis placing LRRCC1 downstream of C2CD3 and SSNA1 in the distal centriole, establishing its recruitment dependencies.

    Evidence KO-validated immunofluorescence, expansion microscopy, interactor screening, and epistasis analysis in human cells (preprint)

    PMID:bio_10.1101_2025.04.28.648957

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Direct vs indirect interactions within the axis not distinguished
    • Stoichiometry and assembly order at molecular resolution unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The biochemical activity of LRRCC1's leucine-rich repeat and coiled-coil domains and the direct molecular interactions through which it organizes the distal centriole remain undefined.
  • No in vitro reconstitution of LRRCC1 binding to microtubules or partners
  • No structural model of the acorn assembly
  • Mechanism of rotationally asymmetric positioning unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005815 microtubule organizing center 2 GO:0005856 cytoskeleton 2 GO:0005929 cilium 2
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-1640170 Cell Cycle 1
Partners
C2CD3SSNA1
Complex memberships
distal centriole 'acorn' (C2CD3–SSNA1–LRRCC1 axis)

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 The VFL1 protein (Chlamydomonas ortholog of LRRCC1) was cloned via a tagged allele and shown to encode a 128 kDa protein with five N-terminal leucine-rich repeat sequences and a large C-terminal alpha-helical coiled-coil domain. Epitope-tagged Vfl1p copurified with basal body flagellar apparatuses, and immunogold labeling localized it inside the lumen of the basal body at the distal end in a rotationally asymmetric pattern, with most gold particles near the doublet microtubules facing the opposite basal body. This established Vfl1p as the first molecular marker of rotational asymmetry in basal bodies and implicated it in establishing correct rotational orientation. Tagged-allele cloning, complementation rescue, co-purification with basal body apparatus, immunofluorescence, immunogold electron microscopy The Journal of cell biology High 11285274
1985 The vfl-1 mutation in Chlamydomonas (VFL1/LRRCC1 locus, Chromosome VIII) causes variable flagellar numbers (0–10 per cell), flagella at non-apical positions, uncoupling of flagellar assembly from the cell cycle, unequal cell divisions, and ultrastructural defects including missing/defective striated fibers and reduced rootlet microtubules, establishing the gene's role in controlling basal body number, positioning, and flagellar apparatus integrity. Genetic mapping, light microscopy, electron microscopy of mutant cells The Journal of cell biology Medium 3972905
1989 Examination of the vfl-1 mutant showed it contains approximately normal levels of centrin and possesses a stable nucleus-basal body connector (NBBC), in contrast to vfl-2 which lacks centrin in the NBBC. This negative result establishes that VFL1 function is distinct from centrin/NBBC integrity, placing Vfl1p in a separate pathway controlling basal body number and positioning. Immunofluorescence with anti-centrin antiserum in mutant strains Cell motility and the cytoskeleton Low 2696598
2008 Human CLERC (LRRCC1), the ortholog of Chlamydomonas Vfl1, is a 1032 aa / 120 kDa centrosomal protein with leucine-rich repeat and coiled-coil domains. Endogenous CLERC associates with centrosomes throughout the cell cycle and accumulates during mitosis. RNAi-mediated depletion caused multipolar spindles and centrosome splitting into fractions containing single centrioles, demonstrating that CLERC maintains centrosome structural integrity to support spindle bipolarity during mitosis. Immunofluorescence localization, RNAi knockdown with spindle morphology and centriole counting readouts Cell cycle (Georgetown, Tex.) Medium 18728398
2019 In planarian flatworms, SMED-VFL1 (ortholog of LRRCC1) is required for assembly of centriole appendages that tether cytoskeletal connectors to position centrioles. Loss of SMED-VFL1 disrupts the asymmetric connections between centrioles and impairs alignment of centrioles along polarity fields, contributing to the bilaterally symmetric pattern of the ventral epidermis. RNAi knockdown in planaria with centriole positioning and polarity readouts Developmental cell Medium 31743665
2022 Using ultrastructure expansion microscopy (U-ExM), human LRRCC1 was shown to localize preferentially to two consecutive triplet microtubules in the distal lumen of human centrioles, revealing rotationally asymmetric positioning. LRRCC1 partially co-localizes with the distal centriole component C2CD3 and affects its recruitment. Depletion of LRRCC1 caused defects in centriole structure, ciliary assembly, and ciliary signaling, establishing LRRCC1 as part of a conserved 'acorn' structure at the distal centriole that cooperates with C2CD3 to organize the distal region and promote primary ciliogenesis. Ultrastructure expansion microscopy (U-ExM), super-resolution imaging, siRNA depletion with ciliary assembly and signaling readouts, co-localization analysis eLife High 35319462
2022 In Xenopus multiciliated cells, Lrrcc1 encodes a basal body component that localizes proximally at the junction with striated rootlets. Morpholino-mediated knockdown of lrrcc1 caused defects in basal body docking, spacing, and polarization, impaired the apical cytoskeleton, and altered ciliary beating, resulting in greatly reduced cilia-powered fluid flow. Morpholino knockdown in Xenopus embryonic ciliated epidermis, immunofluorescence localization, high-speed video microscopy of ciliary beating, fluid flow assays Journal of cell science High 35067717
2013 The vfl1 mutation in Chlamydomonas confers supersensitivity to Taxol, grouping it with other basal body assembly mutants (bld2, bld10, bld12, uni3, vfl2, vfl3), indicating that VFL1 contributes to basal body structural integrity in a manner relevant to microtubule-stabilizing drug sensitivity. Taxol sensitivity assay in mutant strains, double-mutant genetic analysis PloS one Low 23320108
2025 Interactor screening and knockout analysis identified a C2CD3–SSNA1–LRRCC1 hierarchical targeting axis in the distal lumen of human centrioles. LRRCC1 functions downstream of C2CD3 and SSNA1 within this network, placing it in a defined molecular pathway for distal centriole organization and ciliogenesis. KO-validated antibody immunofluorescence, expansion microscopy, interactor screening, epistasis analysis of targeting hierarchy in human cells bioRxivpreprint Medium bio_10.1101_2025.04.28.648957

Source papers

Stage 0 corpus · 22 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Cloning of flagellar genes in Chlamydomonas reinhardtii by DNA insertional mutagenesis. Genetics 191 8244002
2016 Characterizing the morbid genome of ciliopathies. Genome biology 141 27894351
2016 Chronic Exposure to Low Doses of Dioxin Promotes Liver Fibrosis Development in the C57BL/6J Diet-Induced Obesity Mouse Model. Environmental health perspectives 97 27713108
2001 The Vfl1 Protein in Chlamydomonas localizes in a rotationally asymmetric pattern at the distal ends of the basal bodies. The Journal of cell biology 79 11285274
1997 Identification of two amino acids of the human cholecystokinin-A receptor that interact with the N-terminal moiety of cholecystokinin. The Journal of biological chemistry 67 9006937
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
1992 Activated cGMP phosphodiesterase of retinal rods. A complex with transducin alpha subunit. The Journal of biological chemistry 58 1313017
1993 G-protein-effector coupling: a real-time light-scattering assay for transducin-phosphodiesterase interaction. Biochemistry 57 8394130
2022 The glycosaminoglycan interactome 2.0. American journal of physiology. Cell physiology 53 35544698
2004 A comparative expression analysis of gene transcripts in post-fertilization developmental stages of bovine embryos produced in vitro or in vivo. Reproduction in domestic animals = Zuchthygiene 50 15598228
1985 Defective temporal and spatial control of flagellar assembly in a mutant of Chlamydomonas reinhardtii with variable flagellar number. The Journal of cell biology 40 3972905
1992 Enhanced GTPase activity of transducin when bound to cGMP phosphodiesterase in bovine retinal rods. The Journal of biological chemistry 30 1331045
2002 Stage-specific expressed sequence tags obtained during preimplantation bovine development by differential display RT-PCR and suppression subtractive hybridization. Prenatal diagnosis 26 12454973
2019 Emergence of a Bilaterally Symmetric Pattern from Chiral Components in the Planarian Epidermis. Developmental cell 20 31743665
2022 Evolutionary conservation of centriole rotational asymmetry in the human centrosome. eLife 18 35319462
2013 Katanin localization requires triplet microtubules in Chlamydomonas reinhardtii. PloS one 15 23320108
2008 An evolutionarily conserved leucine-rich repeat protein CLERC is a centrosomal protein required for spindle pole integrity. Cell cycle (Georgetown, Tex.) 11 18728398
2022 Lrrcc1 and Ccdc61 are conserved effectors of multiciliated cell function. Journal of cell science 9 35067717
2000 Genetics. Reprogramming X inactivation. Science (New York, N.Y.) 8 11185510
1992 cGMP phosphodiesterase dependent light-induced scattering changes in suspensions of retinal disc membranes. Biochemistry 5 1310620
2022 A two-stage hybrid gene selection algorithm combined with machine learning models to predict the rupture status in intracranial aneurysms. Frontiers in neuroscience 4 36340761
2017 A learned artisan debates the system of the world: Le Clerc versus Mallemant de Messange. British journal for the history of science 0 29019298

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