Affinage

CSPP1

Centrosome and spindle pole-associated protein 1 · UniProt Q1MSJ5

Length
1256 aa
Mass
145.5 kDa
Annotated
2026-06-09
27 papers in source corpus 10 papers cited in narrative 10 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

CSPP1 encodes centrosome and spindle pole–associated isoforms (CSPP and CSPP-L) that function as microtubule-stabilizing factors deployed across mitotic and post-mitotic contexts (PMID:16826565, PMID:36752787). Mechanistically, CSPP1 is deposited within the microtubule lumen, where it preferentially recognizes slowly polymerizing or damaged lattices and caps both plus and minus ends, suppressing intrinsic catastrophe and restricting end dynamics through two separable domains; CSPP1-bound microtubules become resistant to MCAK-mediated depolymerization (PMID:36752787, PMID:38389254). During mitosis CSPP1 localizes to kinetochores and directly binds CENP-H, promoting kinetochore-microtubule stability, damping chromosome oscillation, and supporting spindle assembly checkpoint satisfaction (PMID:26378239). In post-mitotic cells CSPP1 extends into the ciliary axoneme and is required for ciliogenesis, acting through a C-terminal interaction with NPHP8/RPGRIP1L and a ternary complex with NPHP4 at the basal body, and through an intra-ciliary complex with CEP104 that sets axoneme length and licenses Hedgehog signaling competence via Smoothened translocation (PMID:20519441, PMID:31412255). Biallelic truncating mutations in CSPP1 cause Joubert syndrome and related ciliopathies, with patient cells showing reduced and shortened cilia, loss of axonemal ARL13B and adenylyl cyclase III, and impaired SHH signaling (PMID:24360808, PMID:24360803). CSPP-L additionally has a non-ciliary role, localizing to desmosomes in a Desmoplakin-dependent manner to maintain polarized epithelial architecture (PMID:26241740).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2006 Medium

    Established that CSPP1 produces two isoforms targeting centrosomes and spindle poles, with distinct domains controlling microtubule organization and a C-terminal domain mediating centrosome association independent of microtubules.

    Evidence Ectopic expression, domain deletion/mutagenesis, and fluorescence microscopy with cell cycle analysis

    PMID:16826565

    Open questions at the time
    • Did not define the biochemical basis of microtubule binding
    • Endogenous localization and physiological partners not established
  2. 2010 High

    Showed CSPP1 has a ciliary function, localizing to the axoneme and required for ciliogenesis, and physically linking to the NPHP module via its C-terminal domain.

    Evidence Endogenous immunofluorescence, reciprocal co-IP, domain-mapping pulldowns, and siRNA loss-of-function in hTERT-RPE1 cells

    PMID:20519441

    Open questions at the time
    • Ciliogenesis defect was not attributable to NPHP8 loss, leaving the effector mechanism undefined
    • Did not establish how CSPP1 is recruited to the axoneme
  3. 2013 High

    Demonstrated that CSPP1 loss-of-function causes human ciliopathy, connecting its ciliary role to disease and to SHH signaling competence.

    Evidence Biallelic truncating mutations identified in Joubert/Meckel-Gruber patients, patient fibroblast ciliary marker and SHH reporter assays, zebrafish morpholino knockdown

    PMID:24360803 PMID:24360807 PMID:24360808

    Open questions at the time
    • Molecular step at which CSPP1 acts in SHH transduction not pinpointed
    • Tissue-specificity of phenotypes (e.g. absence in nephronophthisis cohort) unexplained
  4. 2015 High

    Defined a mitotic kinetochore function, showing CSPP1 directly binds CENP-H to stabilize kinetochore microtubules and regulate chromosome dynamics.

    Evidence Reciprocal co-IP, in vitro binding, siRNA depletion, live-cell kinetochore tracking, and competing-peptide perturbation

    PMID:26378239

    Open questions at the time
    • Structural basis of CENP-H/CSPP1 binding not resolved
    • Relationship between mitotic and ciliary pools of CSPP1 unclear
  5. 2015 Medium

    Revealed a non-ciliary role in epithelial morphogenesis, with CSPP-L localizing to desmosomes to maintain single-lumen architecture.

    Evidence siRNA knockdown, immunofluorescence, and 3D spheroid culture in non-ciliated Caco-2 cells showing Desmoplakin dependence

    PMID:26241740

    Open questions at the time
    • Direct CSPP-L/Desmoplakin interaction not biochemically validated
    • Mechanism linking desmosomal CSPP-L to ECT2 apical localization unresolved
  6. 2019 High

    Identified the CEP104-CSPP1 ciliary-tip complex as the module controlling axoneme length and Hedgehog signaling competence.

    Evidence Co-IP, siRNA knockdown, Smoothened translocation assay in hTERT-RPE1 cells, and zebrafish cep104 morpholino knockdown

    PMID:31412255

    Open questions at the time
    • How the complex couples length control to Smoothened trafficking not defined
    • CSPP1 recruitment mechanism (CEP104-independent) not identified
  7. 2023 High

    Provided the biochemical and structural mechanism, showing CSPP1 acts from within the microtubule lumen to recognize and stabilize damaged lattices and growing ends through two separate domains.

    Evidence In vitro microtubule reconstitution, fluorescence microscopy, cryo-electron tomography, and domain-deletion analysis

    PMID:36752787

    Open questions at the time
    • Atomic-resolution binding mode within the lumen not resolved
    • How luminal deposition occurs in cells not established
  8. 2024 High

    Extended the stabilization mechanism in cells, showing CSPP1 caps both microtubule ends, suppresses catastrophe, and confers resistance to MCAK depolymerization.

    Evidence Live-cell imaging with laser ablation, gain- and loss-of-function, and a MCAK depolymerization-resistance assay

    PMID:38389254

    Open questions at the time
    • Regulation of CSPP1 end-capping across the cell cycle not defined
    • Interplay with other end-binding/depolymerizing factors not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CSPP1's intrinsic microtubule-stabilizing activity is selectively targeted and regulated across its mitotic (kinetochore), ciliary (axoneme), and epithelial (desmosome) contexts remains unresolved.
  • No unifying mechanism linking luminal microtubule stabilization to context-specific recruitment
  • Isoform-specific functional partitioning (CSPP vs CSPP-L) not fully mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005929 cilium 3 GO:0005856 cytoskeleton 2 GO:0005694 chromosome 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-1640170 Cell Cycle 1
Partners
CENP-HCEP104DSPNPHP4RPGRIP1L
Complex memberships
CEP104-CSPP1 ciliary tip complexCSPP1-NPHP8-NPHP4 ternary complex

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 CSPP and CSPP-L, two splice isoforms encoded by CSPP1, associate with centrosomes and spindle pole microtubules. The coiled-coil mid-domain insertion unique to CSPP-L is required for its differential effects on microtubule organization in mitosis (lagging chromosomes/monopolar spindles vs. multipolar spindles with CSPP). The common C-terminal domain can associate with centrosomes in a microtubule-independent manner and represses microtubule-organization activity until mitosis. Ectopic expression, domain deletion/mutagenesis, fluorescence microscopy, cell cycle analysis Journal of cellular physiology Medium 16826565
2010 CSPP isoforms localize to the ciliary axoneme in post-mitotic resting cells and are required for ciliogenesis in hTERT-RPE1 cells. CSPP isoforms interact via their common C-terminal domain with Nephrocystin 8 (NPHP8/RPGRIP1L) and form a ternary complex with NPHP8 and NPHP4. CSPP-L is required for efficient localization of NPHP8 (but not NPHP4) to the basal body, though the ciliogenesis defect is not mediated through loss of NPHP8. Endogenous protein localization (immunofluorescence), co-immunoprecipitation, siRNA knockdown, domain-mapping pulldown, in vivo tissue immunostaining Molecular biology of the cell High 20519441
2013 Biallelic truncating mutations in CSPP1 cause Joubert syndrome. Patient fibroblasts show reduced numbers and/or shortened primary cilia, reduced axonemal localization of ARL13B and adenylyl cyclase III. Morpholino knockdown of cspp1 in zebrafish reduced ciliary localization of Arl13b and produced curved body, pronephric cysts, and cerebellar abnormalities consistent with JBTS. Patient fibroblast analysis (immunofluorescence for ciliary markers), zebrafish morpholino knockdown American journal of human genetics High 24360808
2013 CSPP1 mutations cause ciliopathy phenotypes ranging from Joubert syndrome to Meckel-Gruber syndrome. Mutant patient fibroblasts display severely impaired ciliogenesis with concomitant defects in sonic hedgehog (SHH) signaling, placing CSPP1 upstream of or at the level of SHH pathway transduction in cilia. Patient fibroblast ciliogenesis assay, SHH signaling reporter assay American journal of human genetics High 24360803
2013 CSPP1 protein localizes to the primary cilium in an in vitro model of human neurogenesis, in addition to centrosomes and spindle poles. CSPP1-mutant fibroblasts from affected individuals show abrogated protein levels and defective ciliogenesis, supporting a neural-specific ciliary function. No CSPP1 mutations were found in a nephronophthisis cohort, indicating tissue-specific ciliary roles. Immunofluorescence localization in human neurogenesis model, patient fibroblast analysis, cohort mutation screening American journal of human genetics Medium 24360807
2015 CSPP1 localizes to kinetochores during mitosis and directly binds CENP-H both in vitro and in vivo. CSPP1 depletion perturbs mitotic progression, compromises spindle assembly checkpoint satisfaction, attenuates chromosome oscillation, and enhances kinetochore movement velocity; CSPP1 overexpression decreases kinetochore movement speed, indicating CSPP1 promotes kinetochore microtubule (kMT) stability. Disruption of CENP-H/CSPP1 interaction with a membrane-permeable competing peptide causes mitotic arrest and chromosome segregation defects. Co-immunoprecipitation, in vitro pulldown/binding assay, siRNA depletion, live-cell imaging of kinetochore movements, competing peptide perturbation The Journal of biological chemistry High 26378239
2015 CSPP-L localizes to desmosomes in apical-basal polarized epithelial cells in a microtubule-independent but Desmoplakin-dependent manner. siRNA depletion of CSPP-L or Desmoplakin promotes multi-lumen spheroid formation in 3D cultures of non-ciliated Caco-2 cells. CSPP-L-depleted multi-lumen spheroids show disrupted apical localization of the cytoskeleton-organizing RhoGEF ECT2, revealing a non-ciliary role in epithelial morphogenesis. siRNA knockdown, immunofluorescence, 3D spheroid culture, subcellular fractionation/localization PloS one Medium 26241740
2019 CSPP1 interacts with the Joubert syndrome ciliary tip protein CEP104 at microtubules to regulate axoneme length. Both CSPP1 and CEP104 are required for ciliary translocation of Smoothened in response to Hedgehog pathway stimulation in hTERT-RPE1 cells. CEP104 is not required for ciliary recruitment of CSPP1, indicating that an intra-ciliary CEP104-CSPP1 complex controls axoneme length and Hedgehog signaling competence. Co-immunoprecipitation, siRNA knockdown, immunofluorescence (Smoothened translocation assay), zebrafish cep104 morpholino knockdown Cell reports High 31412255
2023 In vitro reconstitution showed that CSPP1 preferentially binds to polymerizing microtubule ends growing slowly or undergoing perturbations, stabilizing them similarly to taxane-class compounds. Cryo-electron tomography and fluorescence microscopy demonstrated that CSPP1 is deposited in the microtubule lumen. CSPP1 inhibits microtubule growth and shortening through two separate domains and specifically recognizes and stabilizes damaged microtubule lattices. In vitro microtubule reconstitution assay, fluorescence microscopy, cryo-electron tomography, domain-deletion analysis The Journal of cell biology High 36752787
2024 CSPP1 caps and stabilizes both plus and minus ends of static microtubules in live cells. Real-time imaging of laser-ablated microtubules showed deposition of CSPP1 at newly generated ends with concomitant suppression of dynamic instability. CSPP1 suppresses intrinsic microtubule catastrophe and restricts polymerization at free ends. CSPP1-bound microtubules are resistant to MCAK (mitotic centromere-associated kinesin)-mediated depolymerization. Live-cell imaging, laser ablation of microtubules, CSPP1 overexpression/depletion, functional depolymerization resistance assay Journal of molecular cell biology High 38389254

Source papers

Stage 0 corpus · 27 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Mutations in CSPP1 cause primary cilia abnormalities and Joubert syndrome with or without Jeune asphyxiating thoracic dystrophy. American journal of human genetics 95 24360808
2013 Mutations in CSPP1, encoding a core centrosomal protein, cause a range of ciliopathy phenotypes in humans. American journal of human genetics 71 24360803
2022 Identifies microtubule-binding protein CSPP1 as a novel cancer biomarker associated with ferroptosis and tumor microenvironment. Computational and structural biotechnology journal 68 35832625
2019 circ-CSPP1 promotes proliferation, invasion and migration of ovarian cancer cells by acting as a miR-1236-3p sponge. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 68 30965236
2013 Mutations in CSPP1 lead to classical Joubert syndrome. American journal of human genetics 59 24360807
2000 Changes in cspL, cspP, and cspC mRNA abundance as a function of cold shock and growth phase in Lactobacillus plantarum. Journal of bacteriology 50 10960094
2010 CSPP is a ciliary protein interacting with Nephrocystin 8 and required for cilia formation. Molecular biology of the cell 45 20519441
2019 A CEP104-CSPP1 Complex Is Required for Formation of Primary Cilia Competent in Hedgehog Signaling. Cell reports 41 31412255
2023 CSPP1 stabilizes growing microtubule ends and damaged lattices from the luminal side. The Journal of cell biology 35 36752787
2020 Hsa_circ_CSPP1/MiR-361-5p/ITGB1 Regulates Proliferation and Migration of Cervical Cancer (CC) by Modulating the PI3K-Akt Signaling Pathway. Reproductive sciences (Thousand Oaks, Calif.) 34 32046405
2021 Circ-CSPP1 knockdown suppresses hepatocellular carcinoma progression through miR-493-5p releasing-mediated HMGB1 downregulation. Cellular signalling 30 34182091
2006 CSPP and CSPP-L associate with centrosomes and microtubules and differently affect microtubule organization. Journal of cellular physiology 29 16826565
2020 Circular RNA circ-CSPP1 regulates CCNE2 to facilitate hepatocellular carcinoma cell growth via sponging miR-577. Cancer cell international 19 32514247
2009 Production of membrane proteins for NMR studies using the condensed single protein (cSPP) production system. Journal of structural and functional genomics 19 19856129
2015 Mitotic Protein CSPP1 Interacts with CENP-H Protein to Coordinate Accurate Chromosome Oscillation in Mitosis. The Journal of biological chemistry 17 26378239
2021 Label-free Surface Enhanced Raman Scattering (SERS) on Centrifugal Silver Plasmonic Paper (CSPP): A Novel Methodology for Unprocessed Biofluids Sampling and Analysis. Biosensors 15 34821683
2011 Suppression of phospholipid biosynthesis by cerulenin in the condensed Single-Protein-Production (cSPP) system. Journal of biomolecular NMR 13 21279668
2022 Circ_CSPP1 Regulates the Development of Non-small Cell Lung Cancer via the miR-486-3p/BRD9 Axis. Biochemical genetics 11 35678942
2015 CSPP-L Associates with the Desmosome of Polarized Epithelial Cells and Is Required for Normal Spheroid Formation. PloS one 11 26241740
2014 Nuclear CSPP1 expression defined subtypes of basal-like breast cancer. British journal of cancer 9 24901235
2023 Circular RNA CSPP1 motivates renal cell carcinoma carcinogenesis and the Warburg effect by targeting RAC1 through microRNA-493-5p. Acta biochimica Polonica 8 37722005
2021 Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis. Open life sciences 7 34124372
2020 Roles of circ-CSPP1 on the proliferation and metastasis of glioma cancer. European review for medical and pharmacological sciences 7 32495924
2024 CSPP1 stabilizes microtubules by capping both plus and minus ends. Journal of molecular cell biology 5 38389254
2024 Novel compound heterozygous variants in the CSPP1 gene causes Joubert syndrome: case report and literature review of the CSPP1 gene's pathogenic mechanism. Frontiers in pediatrics 3 38586154
2023 Corrigendum to "Identifies microtubule-binding protein CSPP1 as a novel cancer biomarker associated with ferroptosis and tumor microenvironment" [Comput Struct Biotechnol J 20 (2022) 3322-3335]. Computational and structural biotechnology journal 1 38022700
2020 Correction to: Circular RNA circ-CSPP1 regulates CCNE2 to facilitate hepatocellular carcinoma cell growth via sponging miR-577. Cancer cell international 1 32669969

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