Affinage

CLASP1

CLIP-associating protein 1 · UniProt Q7Z460

Length
1538 aa
Mass
169.5 kDa
Annotated
2026-06-09
22 papers in source corpus 17 papers cited in narrative 17 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

CLASP1 is a microtubule plus-end tracking protein that functions as a local rescue factor, suppressing catastrophes to stabilize microtubule plus ends, and it acts across interphase, mitosis, and meiosis to couple microtubule dynamics to the cell cortex and cytoskeleton (PMID:15631994, PMID:12837247). It directly binds microtubules and EB1 through its middle domain while a separate C-terminal domain mediates microtubule-independent cortical association, with both activities required to promote peripheral microtubule stability (PMID:15631994). During mitosis CLASP1 localizes to the outer kinetochore corona and spindle plus ends and is essential for normal kinetochore and spindle microtubule dynamics (PMID:12837247); at kinetochores it forms temporally regulated, mutually exclusive complexes — first with Kif2b to drive kMT turnover and error correction in early mitosis, then with astrin to promote kMT stability, chromosome alignment, and spindle-checkpoint silencing at metaphase (PMID:20852589). PRC1 recruits CLASP1 to the central spindle at anaphase onset to stabilize anti-parallel midzone microtubules required for cytokinesis (PMID:19561070), and CLASP1 captures astral microtubules at the cell cortex to position the spindle independently of the LGN/NuMA force-generation pathway (PMID:23783028, PMID:21822276). Beyond division, CLASP1 also binds actin filaments to crosslink the actin and microtubule cytoskeletons (PMID:17342765) and supports microtubule-dependent processes including pseudopod-driven cell invasion (PMID:27939686), endothelial tube formation (PMID:23444400), Golgi-based microtubule nucleation and immune-synapse polarization (PMID:41259089), and meiotic spindle organization through associations with PLK1 and DYNC1I1 (PMID:40501366). CLASP1 activity is modulated by GSK3-mediated phosphorylation, which differentially controls CLASP1 versus CLASP2 plus-end decoration (PMID:30787869).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2003 High

    Established that CLASP1 is a kinetochore- and spindle-plus-end factor required to sustain mitotic microtubule dynamics, defining its core role in chromosome segregation.

    Evidence Dominant-negative overexpression and antibody microinjection with live imaging and pharmacological rescue in mammalian cells

    PMID:12837247

    Open questions at the time
    • Molecular partners at the kinetochore not yet identified
    • Mechanism of plus-end stabilization not resolved
  2. 2005 High

    Resolved the molecular basis of CLASP function by mapping direct EB1- and microtubule-binding to the middle domain and cortex-binding to the C-terminus, showing both are needed for peripheral rescue activity.

    Evidence Direct binding assays, domain-deletion analysis, and RNAi rescue with live-cell imaging in HeLa cells

    PMID:15631994

    Open questions at the time
    • Cortical receptor mediating C-terminal anchoring not identified
    • Structural basis of EB1 interaction not determined
  3. 2006 High

    Demonstrated functional redundancy between CLASP1 and CLASP2 in kinetochore and spindle regulation through genetic knockout and cross-rescue.

    Evidence Clasp2 knockout mouse fibroblasts, FRAP, and rescue by ectopic CLASP1/CLASP2

    PMID:16914514

    Open questions at the time
    • Non-redundant isoform-specific functions not delineated
    • Turnover mechanism at kinetochores unexplained
  4. 2007 Medium

    Extended CLASP1 beyond microtubules by showing it binds actin filaments, positioning it as an actin/microtubule crosslinker.

    Evidence Co-immunoprecipitation with actin, FRET, and deletion mapping (CLASP1 by Co-IP only)

    PMID:17342765

    Open questions at the time
    • CLASP1 actin binding shown only by Co-IP, not direct binding/FRET
    • Cellular consequence of crosslinking not established
  5. 2009 High

    Identified PRC1 as the recruiter of CLASP1 to the central spindle, explaining how CLASP1 stabilizes midzone microtubules for cytokinesis.

    Evidence Co-IP, RNAi, and membrane-permeable peptide disruption with immunofluorescence

    PMID:19561070

    Open questions at the time
    • Direct vs indirect PRC1-CLASP1 binding interface not mapped
    • Regulation of recruitment timing not resolved
  6. 2010 High

    Defined a temporal switch in which CLASP1 forms mutually exclusive complexes with Kif2b (error correction) then astrin (stabilization/SAC silencing), linking CLASP1 to checkpoint control.

    Evidence Reciprocal Co-IP, RNAi, and time-lapse imaging of kinetochore parameters

    PMID:20852589

    Open questions at the time
    • Signal triggering the Kif2b-to-astrin switch unknown
    • Stoichiometry of complexes not determined
  7. 2011 Medium

    Placed CLASP1 in cortical astral microtubule capture for spindle positioning, distinct from and upstream of the LGN/NuMA and MAP4 force-generation machinery.

    Evidence RNAi, importazole inhibition, overexpression rescue, and spindle orientation assays (two papers)

    PMID:21822276 PMID:23783028

    Open questions at the time
    • Cortical anchoring partner not identified
    • Relationship to RanGTP pathway only inferred by epistasis
  8. 2012 Medium

    Showed CLASP1 acts downstream of GSK3β to control peripheral MT stabilization and dynein-based retrograde transport, demonstrated via a pathogen internalization model.

    Evidence RNAi, GSK3β pharmacological/genetic epistasis, and lysosome transport assays in T. cruzi infection

    PMID:23107073

    Open questions at the time
    • Direct GSK3β phosphosites on CLASP1 not mapped here
    • Link to dynein/dynactin mechanistically indirect
  9. 2016 Medium

    Established a CLASP1 role in cell invasion by preventing catastrophes at pseudopod tips, enabling microtubule load-bearing in 3D matrices and tumor cell invasion in vivo.

    Evidence RNAi, 3D invasion assays, live MT dynamics imaging, and a mouse cancer model

    PMID:27939686

    Open questions at the time
    • Upstream regulators of pseudopod-tip CLASP1 unknown
    • Single-lab finding
  10. 2013 Medium

    Implicated CLASP1 in vascular morphogenesis through MT assembly, tubulin PTMs, and lumen signaling during endothelial tube formation.

    Evidence siRNA, 3D EC tube assays, tubulin PTM immunofluorescence, and kinase activity assays

    PMID:23444400

    Open questions at the time
    • Direct vs indirect control of the MT1-MMP/Pak/Raf/Erk cascade unclear
    • CLASP1-specific contribution vs EB1/p150Glued not separated
  11. 2019 Medium

    Revealed opposing CLASP1 and CLASP2 functions in neurite extension governed by differential GSK3-mediated phosphorylation sensitivity.

    Evidence RNAi in neuroblastoma, phospho-western blot, and Clasp2 KO primary neurons

    PMID:30787869

    Open questions at the time
    • Molecular basis of opposite outcomes not defined
    • Phosphosite-level regulation not fully mapped
  12. 2025 Medium

    Expanded CLASP1 roles to meiosis, immune-cell cytotoxicity, and Golgi-based MT nucleation, identifying PLK1, DYNC1I1, and AKAP350 associations.

    Evidence Oocyte knockdown with Co-IP (PLK1, DYNC1I1); NK-cell RNAi with cytotoxicity and Golgi-MTOC assays

    PMID:40501366 PMID:41259089

    Open questions at the time
    • Directness of PLK1/DYNC1I1/AKAP350 interactions not all established
    • Mechanism connecting Golgi nucleation to LFA-1 trafficking incomplete
  13. 2025 Low

    Linked CLASP1 loss to radiosensitivity and S-phase/mitotic genome instability in cancer cells.

    Evidence Genome-wide CRISPR screen, CLASP1 knockout, clonogenic survival, and cell cycle analysis

    PMID:40768535

    Open questions at the time
    • Mechanism of DNA protection inferred, not directly established
    • Single study without orthogonal validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the cortical anchoring of CLASP1, the signals driving its temporal partner switches, and the connection between its microtubule rescue activity and genome protection are mechanistically integrated remains unresolved.
  • No identified cortical receptor for the C-terminal domain
  • Regulatory switch controlling Kif2b/astrin exchange unknown
  • DNA-damage protection mechanism uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005794 Golgi apparatus 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
AKAP350ASTRINCD2APDYNC1I1EB1KIF2BPLK1PRC1
Complex memberships
kinetochore

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 CLASP1 (and CLASP2) directly bind EB1 through their middle domain and also bind microtubules directly; the cortex-association of CLASP2 is MT-independent and relies on its C-terminal domain. Both EB1-binding and cortex-binding domains are required to promote MT stability at the cell periphery, where CLASPs act as local rescue factors. RNA interference in HeLa cells, direct binding assays, domain-deletion analysis, live-cell imaging The Journal of cell biology High 15631994
2003 CLASP1 localizes to the outer kinetochore corona and to plus ends of growing spindle microtubules. A truncated dominant-negative form lacking the kinetochore-binding domain causes MT bundles resistant to depolymerization. Microinjection of CLASP1 antibodies suppresses kinetochore and spindle MT dynamics, producing monopolar asters, rescued by MT-stabilizing drugs. Dominant-negative overexpression, antibody microinjection, immunofluorescence, live-cell imaging Cell High 12837247
2010 In early mitosis, CLASP1 forms a complex with Kif2b at kinetochores to promote kMT turnover and error correction; during metaphase, this is replaced by a mutually exclusive CLASP1–astrin complex that promotes kMT stability, chromosome alignment, and SAC silencing. Kif18a affects kMT attachments and chromosome movement through these complexes. Co-immunoprecipitation, RNAi knockdown, kinetochore localization assays, time-lapse imaging The EMBO journal High 20852589
2006 CLASP1 and CLASP2 both localize to kinetochores, centrosomes, and the spindle during mitosis with fast MT-independent turnover; CLASP2 knockout mouse fibroblasts display spindle and chromosome-segregation defects partially rescued by ectopic CLASP1 or CLASP2, demonstrating partial redundancy in regulating kinetochore and spindle function. Clasp2 knockout mouse fibroblasts, FRAP, rescue by ectopic expression, immunofluorescence Molecular biology of the cell High 16914514
2009 PRC1 physically interacts with CLASP1 and recruits it to the central spindle at early anaphase onset. Disruption of the PRC1–CLASP1 interaction (by a membrane-permeable peptide) or CLASP1 repression causes sister-chromatid bridges and depolymerization of spindle midzone microtubules, establishing that PRC1–CLASP1 interaction is required for stable anti-parallel microtubule organization during cytokinesis. Co-immunoprecipitation, RNAi, membrane-permeable peptide disruption, immunofluorescence The Journal of biological chemistry High 19561070
2011 CLASP1 is required to correctly capture astral microtubules at the cell cortex for stable spindle positioning. CLASP1 overexpression rescues spindle-centering defects caused by importazole (RanGTP/importin-β inhibition) without restoring LGN/NuMA localization, indicating CLASP1 stabilizes cortical astral MT contacts independently of the LGN/NuMA force-generation pathway. RNAi depletion, small-molecule inhibition (importazole), overexpression rescue, immunofluorescence, live-cell imaging Molecular biology of the cell Medium 23783028
2011 CLASP1 functions as a microtubule rescue factor at the cell cortex essential for maintaining spindle position and the correct cell-division axis; its role is distinct from MAP4 (which inhibits dynein-dynactin engagement), placing CLASP1 upstream in astral MT capture rather than force-generator regulation. RNAi depletion, live-cell imaging, spindle orientation assays Nature cell biology Medium 21822276
2007 CLASP1α (and CLASP2α) directly bind actin filaments; co-immunoprecipitation with actin and FRET experiments confirm proximity. Both the MT-binding domain and the N-terminal TOG domain of CLASP2α possess actin-binding activity, supporting a role for CLASPs as actin/microtubule crosslinkers. Co-immunoprecipitation with actin, FRET (YFP-CLASP2α / CFP-actin), deletion mapping, live imaging Cell motility and the cytoskeleton Medium 17342765
2016 CLASP1 prevents microtubule catastrophes specifically at the tips of invasive pseudopods, enabling microtubule load-bearing and pseudopod elongation in 3D matrices; CLASP1 depletion impairs mesenchymal cell invasion in 3D culture and in a mouse cancer model without affecting Rho GTPase activity, trafficking, or focal adhesion formation. RNAi knockdown, 3D invasion assays, live MT dynamics imaging, in vivo mouse cancer model Developmental cell Medium 27939686
2012 CLASP1 silencing impairs Trypanosoma cruzi trypomastigote internalization and delays post-entry vacuole fusion and juxtanuclear positioning, correlated with impaired minus-end-directed lysosome transport (mimicking dynactin disruption). GSK3β inhibition enhances T. cruzi entry in a CLASP1-dependent manner, and constitutively active GSK3β dampens infection, placing CLASP1 downstream of GSK3β in controlling peripheral MT stabilization and dynein-based retrograde transport. RNAi knockdown, GSK3β pharmacological inhibition/activation, constitutively-active mutant expression, lysosome transport assays Cellular microbiology Medium 23107073
2019 In neuronal differentiation, CLASP1 and CLASP2 differ in GSK3-mediated phosphorylation sensitivity: GSK3 inhibition reduces CLASP1-decorated MT ends while increasing CLASP2-decorated ends. CLASP1 knockdown causes GSK3 phosphorylation (feedback), and CLASP1 stimulates neurite extension while CLASP2 inhibits it, demonstrating opposite functional roles downstream of differential phosphorylation. RNAi in N1E-115 neuroblastoma cells, western blot (phosphorylation), fluorescence microscopy, Clasp2 KO primary neurons Frontiers in cellular neuroscience Medium 30787869
2013 Clasp1 (together with EB1 and p150Glued) controls endothelial cell tube formation in 3D matrices by inducing microtubule assembly, promoting asymmetric cytoskeletal polarization (acetylated/detyrosinated tubulin subapically, F-actin basally), increasing tubulin acetylation, and regulating an MT1-MMP/Pak/Raf/Erk lumen signaling cascade. siRNA knockdown, 3D EC tube formation assay, immunofluorescence for tubulin modifications, kinase activity assays Blood Medium 23444400
2017 The kinetochore-binding domain of CLASP1 is necessary and sufficient for MT-independent localization to the T. annulata schizont surface (established by transfection of truncation mutants); this interaction is independent of EB1. Overexpression of the CLASP1 MT-binding domain acts as a dominant negative on host MT stability and alters parasite size/morphology. Co-immunoprecipitation shows CLASP1 interacts with schizont membrane protein p104. Truncation mutant transfection, live-cell imaging, MT depolymerization assay, co-immunoprecipitation mSphere Medium 28861517
2018 CLASP1 forms a complex with CD2AP and EB1 at the T. annulata schizont surface throughout the host cell cycle, identified by BioID proximity labeling and co-immunoprecipitation; this complex also integrates bovine adaptor proteins CIN85, 14-3-3ε, and ASAP1 together with schizont membrane protein Ta-p104. BioID proximity labeling, co-immunoprecipitation, fluorescence microscopy Cellular microbiology Medium 29520916
2025 In mouse oocyte meiosis, CLASP1 associates with PLK1 and phosphorylated MAPK1/3; CLASP1 knockdown causes spindle organization and MT-kinetochore attachment defects at metaphase I, increases HDAC6/SIRT1 levels (reducing tubulin acetylation), and disrupts PRC1-based central spindle formation and cytokinesis at telophase I. CLASP1 also interacts with DYNC1I1, which may function downstream as a motor for PLK1 transport. Sibling oocyte knockdown, co-immunoprecipitation (CLASP1–PLK1, CLASP1–DYNC1I1), immunofluorescence, western blot Journal of cell science Medium 40501366
2025 CLASP1/2 depletion in NK cells impairs LFA-1 organization at the immune synapse and blocks centrosome and lytic granule polarization toward the target cell, compromising cytotoxic function. CLASP1/2 and AKAP350 are required for efficient microtubule nucleation at the Golgi (Golgi-MTOC function), and Golgi-derived microtubules contribute to LFA-1 vesicular trafficking to the immune synapse. RNAi depletion in NK cells, immunofluorescence, cytotoxicity assays, Golgi microtubule nucleation assays Journal of leukocyte biology Medium 41259089
2025 CLASP1 knockout in head and neck squamous cell carcinoma cells sensitizes them to radiation (clonogenic assay), causes major defects during S-phase, and results in mitotic cells with broken chromosomes and cell death, suggesting CLASP1 protects against radiation-induced DNA damage through the microtubule machinery. Genome-wide CRISPR-Cas9 screen, CLASP1 knockout, clonogenic survival assay, cell cycle analysis PloS one Low 40768535

Source papers

Stage 0 corpus · 22 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 CLASP1 and CLASP2 bind to EB1 and regulate microtubule plus-end dynamics at the cell cortex. The Journal of cell biology 336 15631994
2003 Human CLASP1 is an outer kinetochore component that regulates spindle microtubule dynamics. Cell 179 12837247
2010 CLASP1, astrin and Kif2b form a molecular switch that regulates kinetochore-microtubule dynamics to promote mitotic progression and fidelity. The EMBO journal 108 20852589
2006 Mammalian CLASP1 and CLASP2 cooperate to ensure mitotic fidelity by regulating spindle and kinetochore function. Molecular biology of the cell 101 16914514
2011 MAP4 and CLASP1 operate as a safety mechanism to maintain a stable spindle position in mitosis. Nature cell biology 99 21822276
2007 Microtubule-binding proteins CLASP1 and CLASP2 interact with actin filaments. Cell motility and the cytoskeleton 76 17342765
2016 Mesenchymal Cell Invasion Requires Cooperative Regulation of Persistent Microtubule Growth by SLAIN2 and CLASP1. Developmental cell 59 27939686
2009 PRC1 cooperates with CLASP1 to organize central spindle plasticity in mitosis. The Journal of biological chemistry 49 19561070
2013 EB1, p150Glued, and Clasp1 control endothelial tubulogenesis through microtubule assembly, acetylation, and apical polarization. Blood 38 23444400
2013 RanGTP and CLASP1 cooperate to position the mitotic spindle. Molecular biology of the cell 32 23783028
2018 Identification and characterisation of a Theileria annulata proline-rich microtubule and SH3 domain-interacting protein (TaMISHIP) that forms a complex with CLASP1, EB1, and CD2AP at the schizont surface. Cellular microbiology 18 29520916
2019 Distinct Functions for Mammalian CLASP1 and -2 During Neurite and Axon Elongation. Frontiers in cellular neuroscience 16 30787869
2017 The Microtubule-Stabilizing Protein CLASP1 Associates with the Theileria annulata Schizont Surface via Its Kinetochore-Binding Domain. mSphere 13 28861517
2012 Host microtubule plus-end binding protein CLASP1 influences sequential steps in the Trypanosoma cruzi infection process. Cellular microbiology 10 23107073
2017 CLASP1 regulates endothelial cell branching morphology and directed migration. Biology open 5 28860131
2024 Multiplex Consanguineous Family Highlights CLASP1 as a Candidate Gene for Lissencephaly. Neurology. Genetics 3 39040917
2025 CLASP1 regulates DYNC1I1 for PLK1-mediated spindle organization and cytokinesis in oocyte meiosis. Journal of cell science 2 40501366
2025 CLASP1/2 REGULATE IMMUNE SYNAPSE MATURATION IN NATURAL KILLER CELLS. bioRxiv : the preprint server for biology 0 39896676
2025 An unexpected role of CLASP1 in radiation response and S-phase regulation of head and neck cancer cells. PloS one 0 40768535
2025 Circular RNA CLASP1 modulates the GLI1/SNAIL axis and enhances macrophage polarization in breast cancer. Oncogene 0 41249488
2025 CLASP1/2 regulate immune synapse maturation in natural killer cells. Journal of leukocyte biology 0 41259089
2017 Erratum for Huber et al., "The Microtubule-Stabilizing Protein CLASP1 Associates with the Theileria annulata Schizont Surface via Its Kinetochore-Binding Domain". mSphere 0 28959741

Missed literature

Know a paper Affinage missed for CLASP1? Flag it for the maintainers and the community.

No submissions yet.