Affinage

CAMSAP2

Calmodulin-regulated spectrin-associated protein 2 · UniProt Q08AD1

Length
1489 aa
Mass
168.1 kDa
Annotated
2026-06-09
17 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CAMSAP2 is a microtubule minus-end binding protein that organizes and stabilizes non-centrosomal microtubule arrays across diverse cell types (PMID:24908486, PMID:23169647). It selectively decorates and protects non-centrosomal minus-ends rather than centrosomal microtubules, and depletion shifts cells toward a radial, centrosome-dominated array with loss of polymerizing plus-ends (PMID:24908486, PMID:23169647). Beyond passive stabilization, CAMSAP2 nucleates microtubules independently of γ-tubulin by co-condensing with αβ-tubulin through phase separation, lowering the nucleation energy barrier and then decorating the resulting lattices (PMID:35762204). In neurons, this minus-end activity establishes neuronal polarity and drives axon specification and dendritic branching (PMID:24908486), in part by anchoring the kinesin-14 motor KIFC3 at dendritic minus-ends to immobilize microtubules (PMID:32084403); in mice, CAMSAP2 loss disrupts mitral cell dendritic remodeling and olfactory circuit formation (PMID:38839944). In epithelial cells CAMSAP2 acts together with CAMSAP3 to maintain the non-centrosomal network and proper organelle positioning (PMID:23169647), and is required specifically for bridging fiber assembly and accurate chromosome segregation during mitosis (PMID:39787108). CAMSAP2 also tethers microtubules to the Golgi: MARK2 phosphorylation at Ser-835 disrupts its interaction with the Golgi-associated protein USO1, impairing Golgi-anchored microtubule organization and Golgi reorientation during directional migration (PMID:40333320). A distinct, microtubule-binding-independent isoform localizes to the Golgi in pancreatic β-cells to promote Golgi-to-ER trafficking and insulin production (PMID:36718359). CAMSAP2 further cooperates with EB1 to tune microtubule dynamics and retrograde autophagosome transport (PMID:28726242).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2012 High

    Established that CAMSAP2 is a minus-end factor that, with CAMSAP3, builds and stabilizes the non-centrosomal microtubule network and controls organelle positioning, answering how cells maintain microtubules away from the centrosome.

    Evidence Immunofluorescence, siRNA single/double depletion, and organelle distribution analysis in epithelial cells

    PMID:23169647

    Open questions at the time
    • Did not resolve how CAMSAP2 versus CAMSAP3 divide labor at minus-ends
    • Mechanism of minus-end recognition not defined
  2. 2014 High

    Defined CAMSAP2's physiological role in neurons by showing its minus-end localization stabilizes non-centrosomal microtubules required for axon specification and dendrite formation, linking minus-end stabilization to neuronal polarity.

    Evidence Live-cell imaging, high-resolution microscopy, laser microsurgery, and RNAi in cultured neurons and in vivo

    PMID:24908486

    Open questions at the time
    • Did not identify the motors or anchors executing minus-end array organization
    • Molecular basis of minus-end protection unresolved
  3. 2017 Medium

    Connected CAMSAP2 to EB1-dependent microtubule dynamics in a transport context, showing CAMSAP2-EB1 association modulates plus-end growth and retrograde autophagosome transport.

    Evidence Co-immunoprecipitation, siRNA knockdown, and live imaging of autophagosome transport in HeLa cells

    PMID:28726242

    Open questions at the time
    • Direct biochemical CAMSAP2-EB1 interaction not structurally characterized
    • Single lab, two methods
  4. 2020 Medium

    Identified KIFC3 as a CAMSAP2 partner that explains how minus-ends are immobilized in dendrites, mechanistically linking a kinesin-14 motor to CAMSAP2-dependent array stabilization.

    Evidence Co-immunoprecipitation, RNAi, and live microtubule dynamics imaging in cultured neurons

    PMID:32084403

    Open questions at the time
    • Co-IP without reciprocal/structural validation
    • Whether anchoring is direct vs. via additional factors unclear
  5. 2022 High

    Demonstrated that CAMSAP2 is not merely a stabilizer but an autonomous, γ-tubulin-independent microtubule nucleator via phase separation with tubulin, redefining its biochemical activity.

    Evidence In vitro reconstitution and phase-separation assays with electron and fluorescence microscopy

    PMID:35762204

    Open questions at the time
    • In vivo contribution of phase-separation nucleation versus templated stabilization not quantified
    • Single lab
  6. 2023 Medium

    Revealed a microtubule-independent moonlighting function: a β-cell-specific CAMSAP2 isoform localizes to the Golgi to support Golgi-ER trafficking and insulin secretion, broadening its functional repertoire beyond minus-ends.

    Evidence Immunofluorescence, siRNA knockdown, Golgi-ER trafficking assay, and insulin measurements in primary β-cells

    PMID:36718359

    Open questions at the time
    • Molecular mechanism of Golgi targeting of this isoform unknown
    • Trafficking partners at the Golgi not identified
  7. 2025 Medium

    Established phospho-regulation of CAMSAP2 by MARK2 at Ser-835 that controls Golgi-anchored microtubules and migration by tuning USO1 binding, defining an upstream switch on its Golgi function.

    Evidence Mass spectrometry phospho-mapping, mutagenesis, Co-IP differential binding, and live imaging of Golgi reorientation

    PMID:40333320

    Open questions at the time
    • Whether USO1 binding is direct not shown structurally
    • Single lab
  8. 2025 Medium

    Showed a non-redundant mitotic role for CAMSAP2 in bridging fiber assembly and faithful chromosome segregation, distinguishing it from CAMSAP3 in spindle function.

    Evidence CRISPR knockout, live-cell mitosis imaging, spindle morphometry, and segregation analysis in Caco-2 cells

    PMID:39787108

    Open questions at the time
    • How CAMSAP2 contributes to bridging fiber minus-ends mechanistically unresolved
    • Single cell line

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CAMSAP2's intrinsic minus-end stabilization, phase-separation nucleation, and Golgi-anchoring activities are coordinated and regulated across distinct cell types remains unresolved, as does the structural basis of its minus-end and partner recognition.
  • No structure of CAMSAP2 on minus-ends
  • Relative in vivo contribution of nucleation vs. stabilization unknown
  • Isoform-specific functional partitioning incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 2
Localization
GO:0005794 Golgi apparatus 3 GO:0005856 cytoskeleton 3 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-1640170 Cell Cycle 1 R-HSA-9612973 Autophagy 1
Partners
CAMSAP3EB1KIFC3MARK2USO1

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 CAMSAP2 specifically localizes to non-centrosomal microtubule minus-ends in neurons (not centrosomal MTs), stabilizes these minus-ends, and is required for neuronal polarity, axon specification, and dendritic branch formation in vitro and in vivo. Live-cell imaging, high-resolution microscopy, and laser-based microsurgery established this localization and function. Live-cell imaging, high-resolution microscopy, laser-based microsurgery, RNAi knockdown in cultured neurons and in vivo Neuron High 24908486
2012 CAMSAP2 and CAMSAP3 (Nezha) co-cluster at minus-ends of noncentrosomal microtubules in epithelial cells and cooperate to stabilize them; depletion of both CAMSAPs causes loss of polymerizing plus-ends, compensatory centrosomal microtubule growth, and mislocalization of early endosomes and the Golgi apparatus. Immunofluorescence, siRNA depletion, organelle distribution analysis in epithelial cells Proceedings of the National Academy of Sciences of the United States of America High 23169647
2022 CAMSAP2 acts as a microtubule nucleator by co-condensing with αβ-tubulin via phase separation, reducing the nucleation energy barrier, generating aster-like structures in vitro, and then decorating the radiating microtubule lattices—providing a γ-tubulin-independent nucleation centre. In vitro reconstitution assay, phase-separation assay, electron microscopy, fluorescence microscopy eLife High 35762204
2020 CAMSAP2 interacts with the kinesin-14 motor KIFC3, which has a dendrite-specific distribution. CAMSAP2 anchors KIFC3 at microtubule minus-ends to immobilize microtubule arrays in dendrites; depletion of either KIFC3 or CAMSAP2 increases microtubule dynamics during dendritic development. Co-immunoprecipitation, RNAi knockdown, live-cell microtubule dynamics imaging in cultured neurons Current biology : CB Medium 32084403
2020 In hepatocellular carcinoma cells, CAMSAP2 cooperates with EB1 to regulate microtubule dynamics and invasive cell migration via Trio/Rac1 signaling; CAMSAP2 depletion transforms the noncentrosomal microtubule array into a radial centrosomal pattern and strongly reduces acetylated microtubule abundance. Mechanistically, CAMSAP2 activates c-Jun to repress HDAC6 transcription through the Trio-dependent Rac1/JNK pathway, thereby increasing microtubule acetylation. Co-immunoprecipitation, immunofluorescence, western blotting, ChIP, luciferase reporter assay, siRNA knockdown, in vivo orthotopic metastasis model Theranostics Medium 32206120
2017 CAMSAP2 regulates retrograde autophagosome transport by controlling microtubule dynamics and cooperating with EB1; an association between CAMSAP2 and EB1 in the cytosol modulates EB1 binding to MT plus-ends, affecting MT growth directions and autophagosome transport. Co-immunoprecipitation, siRNA knockdown, live-cell imaging of autophagosome transport in HeLa cells FEBS letters Medium 28726242
2023 In primary pancreatic β-cells, CAMSAP2 localizes predominantly to the Golgi apparatus (not microtubule minus-ends) in an isoform-dependent and microtubule-binding-independent manner, and promotes Golgi-to-ER trafficking to support insulin production; knockdown reduces total insulin content and attenuates glucose-stimulated insulin secretion. Immunofluorescence localization, siRNA knockdown, Golgi-ER trafficking assay, insulin content and secretion measurement in primary β-cells iScience Medium 36718359
2025 MARK2 kinase phosphorylates CAMSAP2 at serine-835; this phosphorylation specifically disrupts CAMSAP2's interaction with the Golgi-associated protein USO1 (but not CG-NAP or CLASPs), impairing microtubule anchoring to the Golgi, altering microtubule polarity distribution, and blocking Golgi reorientation during directional cell migration. Mass spectrometry phospho-mapping, co-immunoprecipitation, mutagenesis, live-cell imaging of Golgi reorientation eLife Medium 40333320
2025 CAMSAP2 (but not CAMSAP3) is required for bridging fiber assembly during mitosis in human Caco-2 epithelial cells; CAMSAP2 KO cells show delayed mitotic progression, a short spindle with reduced microtubule density around chromosomes, loss of bridging fibers, slow anaphase spindle elongation, and chromosome segregation errors. CAMSAP2 knockout (CRISPR), live-cell imaging of mitosis, spindle morphometry, chromosome segregation analysis PloS one Medium 39787108
2024 CAMSAP2 deficiency in mice impairs dendritic remodeling of mitral cells in the olfactory bulb, disrupts olfactory circuit formation, causes olfactory deficits, and renders males infertile due to mating behavior defects (reproductive tract is morphologically normal). Camsap2 knockout mice, olfactory behavioral assays, morphological analysis of mitral cell dendrites, immunofluorescence EMBO reports Medium 38839944
2013 CAMSAP2 (CAMSAP1L1) co-localizes partially with β-tubulin in neuroblastoma cells; siRNA-mediated knockdown of CAMSAP2 stimulates neurite outgrowth (increased total length, number of processes, and branches), indicating CAMSAP2 represses neurite outgrowth. siRNA knockdown in SH-SY5Y cells, immunofluorescence co-localization, neurite morphometry Neuroscience letters Low 24148305
2023 CAMSAP2 interacts with RASAL2 and facilitates its degradation through the ubiquitin-proteasome system, thereby activating ERK signaling and promoting lung cancer cell migration and metastasis. Co-immunoprecipitation, proteomic analysis, ubiquitin-proteasome pathway assays, siRNA knockdown, in vivo tail-vein metastasis model Life sciences Low 38159595
2022 CAMSAP2 activates JNK/c-Jun signaling and upregulates MMP-1 transcription to promote colorectal cancer cell migration and invasion; gain- and loss-of-function experiments identified MMP-1 as a downstream effector. siRNA knockdown and overexpression, wound-healing and transwell assays, western blotting for JNK/c-Jun/MMP-1, in vivo lung metastasis model Scientific reports Low 36207462

Source papers

Stage 0 corpus · 17 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development. Neuron 178 24908486
2012 Nezha/CAMSAP3 and CAMSAP2 cooperate in epithelial-specific organization of noncentrosomal microtubules. Proceedings of the National Academy of Sciences of the United States of America 131 23169647
2011 Two-stage genome-wide association study identifies variants in CAMSAP1L1 as susceptibility loci for epilepsy in Chinese. Human molecular genetics 61 22116939
2020 Microtubule Minus-End Binding Protein CAMSAP2 and Kinesin-14 Motor KIFC3 Control Dendritic Microtubule Organization. Current biology : CB 34 32084403
2020 CAMSAP2-mediated noncentrosomal microtubule acetylation drives hepatocellular carcinoma metastasis. Theranostics 30 32206120
2022 CAMSAP2 organizes a γ-tubulin-independent microtubule nucleation centre through phase separation. eLife 28 35762204
2019 CAMSAP2 Is a Microtubule Minus-End Targeting Protein That Regulates BTB Dynamics Through Cytoskeletal Organization. Endocrinology 23 30994903
2022 CAMSAP2 promotes colorectal cancer cell migration and invasion through activation of JNK/c-Jun/MMP-1 signaling pathway. Scientific reports 21 36207462
2023 CAMSAP2 localizes to the Golgi in islet β-cells and facilitates Golgi-ER trafficking. iScience 7 36718359
2017 Noncentrosomal microtubules regulate autophagosome transport through CAMSAP2-EB1 cross-talk. FEBS letters 7 28726242
2023 CAMSAP2 enhances lung cancer cell metastasis by mediating RASAL2 degradation. Life sciences 5 38159595
2013 The potential role of CAMSAP1L1 in symptomatic epilepsy. Neuroscience letters 5 24148305
2023 [High expression of CAMSAP2 promotes invasion and metastasis of gastric cancer cells by upregulating TGF-β signaling]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 4 37814859
2025 CAMSAP2 is required for bridging fiber assembly to ensure mitotic spindle assembly and chromosome segregation in human epithelial Caco-2 cells. PloS one 1 39787108
2024 Deficiency of CAMSAP2 impairs olfaction and the morphogenesis of mitral cells. EMBO reports 1 38839944
2026 miR-145-5p/CAMSAP2 axis modulates cisplatin sensitivity in non-small cell lung cancer. Cancer cell international 0 41620802
2025 MARK2 regulates Golgi apparatus reorientation by phosphorylation of CAMSAP2 in directional cell migratio. eLife 0 40333320

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