Affinage

CSPP1

Centrosome and spindle pole-associated protein 1 · UniProt Q1MSJ5

Length
1256 aa
Mass
145.5 kDa
Annotated
2026-04-28
27 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CSPP1 is a centrosome-, cilium-, and kinetochore-associated protein that stabilizes microtubules through luminal deposition and end-capping, and is essential for ciliogenesis, ciliary signaling, and accurate chromosome segregation. CSPP1 preferentially binds slowly growing or damaged microtubule ends and lattices, where it suppresses both catastrophe and polymerization through separable domains, rendering microtubules resistant to MCAK-mediated depolymerization (PMID:36752787, PMID:38389254). It forms an intra-ciliary complex with CEP104 to regulate axoneme length and is required for Smoothened translocation during Hedgehog signaling, while interacting with NPHP8/RPGRIP1L to support basal body organization and ciliogenesis (PMID:31412255, PMID:20519441). Loss-of-function mutations in CSPP1 cause Joubert syndrome and related ciliopathies, with patient fibroblasts showing severely impaired ciliogenesis, reduced ciliary ARL13B localization, and defective Sonic Hedgehog signaling (PMID:24360808, PMID:24360803).

Mechanistic history

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

    Establishing that CSPP1 is a centrosome/spindle-associated protein with cell-cycle-regulated localization answered where the protein acts and revealed its connection to microtubule organization during mitosis.

    Evidence Ectopic expression and live-cell imaging of CSPP isoforms with domain deletion analysis in cultured cells

    PMID:16826565

    Open questions at the time
    • Overexpression-based study without loss-of-function validation
    • No endogenous protein dynamics characterized
    • No interacting partners identified
  2. 2010 High

    Demonstrating that CSPP1 localizes to the ciliary axoneme, is required for ciliogenesis, and physically interacts with nephrocystin-8 (NPHP8/RPGRIP1L) extended its function beyond mitosis to primary cilia biology and linked it to the nephrocystin complex.

    Evidence siRNA knockdown in hTERT-RPE1 cells, reciprocal co-immunoprecipitation, immunofluorescence for ciliogenesis and basal body markers

    PMID:20519441

    Open questions at the time
    • Mechanism by which CSPP1 promotes ciliogenesis not defined
    • NPHP8 interaction domain not mapped in detail
    • No in vivo model tested
  3. 2013 High

    Identification of CSPP1 mutations in Joubert syndrome patients, combined with demonstration of impaired ciliogenesis, reduced ciliary ARL13B, and defective Sonic Hedgehog signaling in patient cells and zebrafish, established CSPP1 as a ciliopathy gene and placed it upstream of Hedgehog pathway activation.

    Evidence Patient fibroblast ciliogenesis and SHH reporter assays, zebrafish morpholino knockdown with Arl13b localization analysis

    PMID:24360803 PMID:24360807 PMID:24360808

    Open questions at the time
    • Precise step in ciliogenesis blocked by CSPP1 loss not defined
    • Neural-specific cilia function inferred from limited models
    • No rescue experiments reported
  4. 2015 High

    Discovery that CSPP1 interacts with the kinetochore protein CENP-H and promotes kinetochore-microtubule stability revealed a second, mitosis-specific function distinct from its ciliary role, explaining how its loss causes chromosome segregation defects.

    Evidence Co-immunoprecipitation, in vitro binding assay, siRNA knockdown with live-cell kinetochore tracking, competing peptide perturbation

    PMID:26378239

    Open questions at the time
    • How CSPP1 is recruited to kinetochores versus cilia remains unclear
    • No structural detail of the CENP-H/CSPP1 interface
    • Relationship between kinetochore and ciliary functions not dissected
  5. 2015 Medium

    Localization of CSPP-L to desmosomes in polarized epithelia and its requirement for single-lumen morphogenesis uncovered a non-ciliary, non-mitotic role in epithelial polarity.

    Evidence siRNA knockdown in 3D spheroid cultures, immunofluorescence, fractionation showing Desmoplakin-dependent localization

    PMID:26241740

    Open questions at the time
    • Mechanism linking desmosome localization to lumen formation unclear
    • Single lab; not independently replicated
    • Relationship to ciliary and kinetochore functions of CSPP1 not explored
  6. 2019 High

    Identification of the CSPP1–CEP104 intra-ciliary complex and its requirement for axoneme length regulation and Smoothened translocation during Hedgehog signaling provided the molecular basis for CSPP1's ciliary signaling function.

    Evidence Reciprocal co-immunoprecipitation, siRNA knockdown in hTERT-RPE1 cells, Hedgehog-stimulated SMO translocation assay, zebrafish morpholino

    PMID:31412255

    Open questions at the time
    • How the CSPP1–CEP104 complex regulates axoneme length mechanistically is unclear
    • Stoichiometry and structure of the complex not determined
    • Whether other ciliary tip proteins participate is unknown
  7. 2023 High

    In vitro reconstitution and cryo-electron tomography revealed that CSPP1 is deposited in the microtubule lumen at slowly growing ends and at damaged lattice sites, using separable domains to inhibit growth and shortening — establishing its molecular mechanism as an intraluminal microtubule stabilizer.

    Evidence In vitro reconstitution with purified proteins, fluorescence microscopy, cryo-ET, domain mutant analysis

    PMID:36752787

    Open questions at the time
    • How luminal deposition occurs mechanistically is unresolved
    • In vivo relevance of lattice-damage recognition not tested
    • Whether luminal occupancy explains all ciliary and kinetochore phenotypes is unknown
  8. 2024 High

    Live-cell laser ablation and in vitro assays demonstrated that CSPP1 caps and stabilizes both plus and minus ends of static microtubules, conferring resistance to MCAK-mediated depolymerization, thereby unifying its end-stabilization activity with the protection of microtubules during mitosis and interphase.

    Evidence Real-time live-cell imaging with laser ablation, CSPP1 overexpression/depletion, in vitro microtubule dynamics assays

    PMID:38389254

    Open questions at the time
    • Structural basis for MCAK resistance not determined
    • Contribution of minus-end capping versus luminal deposition to each cellular function not separated
    • How CSPP1 activity is regulated at different cell cycle stages remains unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how CSPP1's intraluminal microtubule stabilization is partitioned between its ciliary, kinetochore, and desmosomal functions, and how its activity is cell-cycle regulated to switch between these contexts.
  • No structure of CSPP1 or its complexes at atomic resolution
  • Regulatory post-translational modifications controlling context-dependent localization not identified
  • Genotype–phenotype correlation for different CSPP1 mutations in ciliopathy patients incompletely understood

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4
Localization
GO:0005929 cilium 4 GO:0005856 cytoskeleton 3 GO:0005815 microtubule organizing center 2 GO:0005694 chromosome 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-162582 Signal Transduction 2
Partners
CENPHCEP104DSPNPHP4RPGRIP1L
Complex memberships
CSPP1–CEP104 ciliary tip complexCSPP1–NPHP8–NPHP4 complex

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 CSPP and CSPP-L associate with centrosomes and microtubules; CSPP-L relocates from spindle microtubules/poles in metaphase to the mid-spindle in anaphase and mid-body in telophase/cytokinesis. The coiled-coil mid-domain insertion differentially affects microtubule organization, while the common C-terminal domain represses that activity until mitosis and can associate with centrosomes in a microtubule-independent manner. Ectopic expression, live-cell imaging, domain deletion/mutant analysis Journal of cellular physiology Medium 16826565
2010 CSPP isoforms localize to the cilia axoneme in postmitotic cells and are required for ciliogenesis in hTERT-RPE1 cells. CSPP isoforms interact via their common C-terminal domain with Nephrocystin 8 (NPHP8/RPGRIP1L) to form a ternary complex with NPHP4, and CSPP-L is required for efficient localization of NPHP8 but not NPHP4 to the basal body. siRNA knockdown, co-immunoprecipitation, immunofluorescence localization, in vitro ciliogenesis assay Molecular biology of the cell High 20519441
2013 Loss of CSPP1 function in human fibroblasts reduces numbers and length of primary cilia and diminishes axonemal localization of ARL13B and adenylyl cyclase III. Morpholino knockdown of cspp1 in zebrafish reduces ciliary localization of Arl13b and causes JBTS-related phenotypes. Patient fibroblast analysis, morpholino knockdown in zebrafish, immunofluorescence American journal of human genetics High 24360803 24360807 24360808
2013 CSPP1 mutations in patient fibroblasts cause severely impaired ciliogenesis with concomitant defects in sonic hedgehog (SHH) signaling, placing CSPP1 upstream of SHH pathway activation. Patient fibroblast ciliogenesis assay, SHH signaling reporter assay American journal of human genetics Medium 24360803
2013 CSPP1 protein localizes to the primary cilium in an in vitro model of human neurogenesis, and its loss abrogates ciliogenesis in neural cell contexts, suggesting a neural-specific function of primary cilia. Immunofluorescence localization in neurogenesis model, patient fibroblast analysis American journal of human genetics Medium 24360807
2015 CSPP1 localizes to kinetochores and interacts with CENP-H in vitro and in vivo. Depletion of CSPP1 attenuates chromosome oscillation, enhances kinetochore movement velocity, and causes spindle assembly checkpoint defects. Disruption of CENP-H/CSPP1 interaction using a competing peptide causes mitotic arrest and chromosome segregation defects, indicating CSPP1 promotes kinetochore microtubule (kMT) stability. Co-immunoprecipitation, in vitro binding assay, siRNA knockdown, live-cell imaging of kinetochore dynamics, 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 and disrupts apical junction localization of RhoGEF ECT2, revealing a non-ciliary role in epithelial morphogenesis. siRNA knockdown, 3D spheroid culture, immunofluorescence, fractionation PloS one Medium 26241740
2019 CSPP1 interacts with CEP104 at microtubules to form an intra-ciliary complex that regulates axoneme length. Both CSPP1 and CEP104 are required for Smoothened translocation to cilia in response to Hedgehog pathway stimulation, but CEP104 is not required for ciliary recruitment of CSPP1. Co-immunoprecipitation, siRNA knockdown in hTERT-RPE1 cells, Hedgehog signaling assay (SMO translocation), zebrafish morpholino knockdown Cell reports High 31412255
2023 CSPP1 preferentially binds to slowly growing or perturbed polymerizing microtubule ends and is deposited in the microtubule lumen, where it inhibits microtubule growth and shortening through two separate domains. CSPP1 also specifically recognizes and stabilizes damaged microtubule lattices. In vitro reconstitution assay, fluorescence microscopy, cryo-electron tomography, domain mutant analysis The Journal of cell biology High 36752787
2024 CSPP1 caps and stabilizes both plus and minus ends of static microtubules, suppressing catastrophe and restricting polymerization. CSPP1-bound microtubules are resistant to mitotic centromere-associated kinesin (MCAK)-mediated depolymerization. Laser ablation experiments in live cells showed CSPP1 deposits at newly generated microtubule ends and concomitantly suppresses their dynamic instability. Real-time live-cell imaging, laser ablation, CSPP1 overexpression/depletion, in vitro microtubule 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
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
2022 Identifies microtubule-binding protein CSPP1 as a novel cancer biomarker associated with ferroptosis and tumor microenvironment. Computational and structural biotechnology journal 64 35832625
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 49 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 40 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 14 34821683
2011 Suppression of phospholipid biosynthesis by cerulenin in the condensed Single-Protein-Production (cSPP) system. Journal of biomolecular NMR 13 21279668
2015 CSPP-L Associates with the Desmosome of Polarized Epithelial Cells and Is Required for Normal Spheroid Formation. PloS one 11 26241740
2022 Circ_CSPP1 Regulates the Development of Non-small Cell Lung Cancer via the miR-486-3p/BRD9 Axis. Biochemical genetics 10 35678942
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