{"gene":"CAMSAP2","run_date":"2026-06-09T22:57:17","timeline":{"discoveries":[{"year":2014,"finding":"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.","method":"Live-cell imaging, high-resolution microscopy, laser-based microsurgery, RNAi knockdown in cultured neurons and in vivo","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (live imaging, microsurgery, in vitro and in vivo KD), replicated in the field","pmids":["24908486"],"is_preprint":false},{"year":2012,"finding":"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.","method":"Immunofluorescence, siRNA depletion, organelle distribution analysis in epithelial cells","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal localization, double-depletion epistasis, organelle readout with multiple methods","pmids":["23169647"],"is_preprint":false},{"year":2022,"finding":"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.","method":"In vitro reconstitution assay, phase-separation assay, electron microscopy, fluorescence microscopy","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution with direct biochemical and structural imaging, single lab but multiple orthogonal methods","pmids":["35762204"],"is_preprint":false},{"year":2020,"finding":"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.","method":"Co-immunoprecipitation, RNAi knockdown, live-cell microtubule dynamics imaging in cultured neurons","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP interaction and KD phenotype with dynamics readout, single lab","pmids":["32084403"],"is_preprint":false},{"year":2020,"finding":"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.","method":"Co-immunoprecipitation, immunofluorescence, western blotting, ChIP, luciferase reporter assay, siRNA knockdown, in vivo orthotopic metastasis model","journal":"Theranostics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (Co-IP, ChIP, luciferase, in vivo), single lab","pmids":["32206120"],"is_preprint":false},{"year":2017,"finding":"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.","method":"Co-immunoprecipitation, siRNA knockdown, live-cell imaging of autophagosome transport in HeLa cells","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP interaction and KD with transport readout, single lab, two orthogonal methods","pmids":["28726242"],"is_preprint":false},{"year":2023,"finding":"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.","method":"Immunofluorescence localization, siRNA knockdown, Golgi-ER trafficking assay, insulin content and secretion measurement in primary β-cells","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization with functional consequence (trafficking, insulin content), multiple readouts, single lab","pmids":["36718359"],"is_preprint":false},{"year":2025,"finding":"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.","method":"Mass spectrometry phospho-mapping, co-immunoprecipitation, mutagenesis, live-cell imaging of Golgi reorientation","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — MS-identified phosphosite, mutagenesis, Co-IP differential binding, functional Golgi readout; single lab","pmids":["40333320"],"is_preprint":false},{"year":2025,"finding":"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.","method":"CAMSAP2 knockout (CRISPR), live-cell imaging of mitosis, spindle morphometry, chromosome segregation analysis","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with multiple defined mitotic phenotypes, live imaging; single lab","pmids":["39787108"],"is_preprint":false},{"year":2024,"finding":"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).","method":"Camsap2 knockout mice, olfactory behavioral assays, morphological analysis of mitral cell dendrites, immunofluorescence","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO mouse with specific behavioral and morphological phenotype readouts; single lab","pmids":["38839944"],"is_preprint":false},{"year":2013,"finding":"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.","method":"siRNA knockdown in SH-SY5Y cells, immunofluorescence co-localization, neurite morphometry","journal":"Neuroscience letters","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single KD method with morphometric readout, no pathway mechanism","pmids":["24148305"],"is_preprint":false},{"year":2023,"finding":"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.","method":"Co-immunoprecipitation, proteomic analysis, ubiquitin-proteasome pathway assays, siRNA knockdown, in vivo tail-vein metastasis model","journal":"Life sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — Co-IP and biochemical degradation assay in single lab, limited mechanistic validation of the ubiquitin pathway","pmids":["38159595"],"is_preprint":false},{"year":2022,"finding":"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.","method":"siRNA knockdown and overexpression, wound-healing and transwell assays, western blotting for JNK/c-Jun/MMP-1, in vivo lung metastasis model","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — pathway placement by KD/OE phenotype, single lab, no direct binding or enzymatic assay","pmids":["36207462"],"is_preprint":false}],"current_model":"CAMSAP2 is a microtubule minus-end binding protein that stabilizes non-centrosomal microtubules by decorating and protecting their minus-ends; it also acts as a γ-tubulin-independent microtubule nucleator through phase separation with αβ-tubulin. In neurons, CAMSAP2 organizes non-centrosomal microtubule arrays to control axon specification, dendritic development, and mitral cell morphogenesis, partly by anchoring the kinesin-14 motor KIFC3 at minus-ends in dendrites. In epithelial cells, CAMSAP2 cooperates with CAMSAP3 to maintain non-centrosomal microtubule networks and suppress centrosomal microtubule growth, and is required for bridging fiber assembly during mitosis. CAMSAP2 anchors microtubules to the Golgi apparatus and its phosphorylation by MARK2 at Ser-835 regulates Golgi reorientation during cell migration by modulating interaction with USO1. In pancreatic β-cells, a distinct CAMSAP2 isoform localizes to the Golgi independently of microtubule binding and promotes Golgi-ER trafficking. Additionally, CAMSAP2 cross-talks with EB1 to regulate microtubule dynamics, autophagosome transport, and cancer cell invasiveness via Trio/Rac1/JNK signaling."},"narrative":{"mechanistic_narrative":"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].","teleology":[{"year":2012,"claim":"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","pmids":["23169647"],"confidence":"High","gaps":["Did not resolve how CAMSAP2 versus CAMSAP3 divide labor at minus-ends","Mechanism of minus-end recognition not defined"]},{"year":2014,"claim":"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","pmids":["24908486"],"confidence":"High","gaps":["Did not identify the motors or anchors executing minus-end array organization","Molecular basis of minus-end protection unresolved"]},{"year":2017,"claim":"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","pmids":["28726242"],"confidence":"Medium","gaps":["Direct biochemical CAMSAP2-EB1 interaction not structurally characterized","Single lab, two methods"]},{"year":2020,"claim":"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","pmids":["32084403"],"confidence":"Medium","gaps":["Co-IP without reciprocal/structural validation","Whether anchoring is direct vs. via additional factors unclear"]},{"year":2022,"claim":"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","pmids":["35762204"],"confidence":"High","gaps":["In vivo contribution of phase-separation nucleation versus templated stabilization not quantified","Single lab"]},{"year":2023,"claim":"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","pmids":["36718359"],"confidence":"Medium","gaps":["Molecular mechanism of Golgi targeting of this isoform unknown","Trafficking partners at the Golgi not identified"]},{"year":2025,"claim":"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","pmids":["40333320"],"confidence":"Medium","gaps":["Whether USO1 binding is direct not shown structurally","Single lab"]},{"year":2025,"claim":"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","pmids":["39787108"],"confidence":"Medium","gaps":["How CAMSAP2 contributes to bridging fiber minus-ends mechanistically unresolved","Single cell line"]},{"year":null,"claim":"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.","evidence":"No single study integrates these activities or provides a structural model","pmids":[],"confidence":"Low","gaps":["No structure of CAMSAP2 on minus-ends","Relative in vivo contribution of nucleation vs. stabilization unknown","Isoform-specific functional partitioning incompletely mapped"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,1,2,3]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,7]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1,6,7]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[5]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[1,2]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[8]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[5]}],"complexes":[],"partners":["CAMSAP3","KIFC3","EB1","USO1","MARK2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q08AD1","full_name":"Calmodulin-regulated spectrin-associated protein 2","aliases":["Calmodulin-regulated spectrin-associated protein 1-like protein 1"],"length_aa":1489,"mass_kda":168.1,"function":"Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:23169647, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In addition, it also reduces the velocity of microtubule polymerization (PubMed:24486153, PubMed:24706919). Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes (PubMed:27666745). Essential for the tethering, but not for nucleation of non-centrosomal microtubules at the Golgi: together with Golgi-associated proteins AKAP9 and PDE4DIP, required to tether non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745). Also acts as a regulator of neuronal polarity and development: localizes to non-centrosomal microtubule minus-ends in neurons and stabilizes non-centrosomal microtubules, which is required for neuronal polarity, axon specification and dendritic branch formation (PubMed:24908486). Through the microtubule cytoskeleton, regulates the autophagosome transport (PubMed:28726242)","subcellular_location":"Cytoplasm, cytoskeleton; Golgi apparatus; Cytoplasm, cytoskeleton, cilium basal body; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q08AD1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CAMSAP2","classification":"Not Classified","n_dependent_lines":59,"n_total_lines":1208,"dependency_fraction":0.048841059602649006},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"TUBB4B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/CAMSAP2","total_profiled":1310},"omim":[{"mim_id":"613775","title":"CALMODULIN-REGULATED SPECTRIN-ASSOCIATED PROTEIN 2; CAMSAP2","url":"https://www.omim.org/entry/613775"},{"mim_id":"611786","title":"MEDIATOR OF CELL MOTILITY 1; MEMO1","url":"https://www.omim.org/entry/611786"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Microtubule ends","reliability":"Supported"},{"location":"Golgi apparatus","reliability":"Additional"},{"location":"Primary cilium","reliability":"Additional"},{"location":"Basal body","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CAMSAP2"},"hgnc":{"alias_symbol":["KIAA1078"],"prev_symbol":["CAMSAP1L1"]},"alphafold":{"accession":"Q08AD1","domains":[{"cath_id":"-","chopping":"15-152","consensus_level":"medium","plddt":89.9072,"start":15,"end":152},{"cath_id":"3.10.20.360","chopping":"1363-1469","consensus_level":"high","plddt":89.8854,"start":1363,"end":1469}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q08AD1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q08AD1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q08AD1-F1-predicted_aligned_error_v6.png","plddt_mean":56.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CAMSAP2","jax_strain_url":"https://www.jax.org/strain/search?query=CAMSAP2"},"sequence":{"accession":"Q08AD1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q08AD1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q08AD1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q08AD1"}},"corpus_meta":[{"pmid":"24908486","id":"PMC_24908486","title":"Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development.","date":"2014","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/24908486","citation_count":178,"is_preprint":false},{"pmid":"23169647","id":"PMC_23169647","title":"Nezha/CAMSAP3 and CAMSAP2 cooperate in epithelial-specific organization of noncentrosomal microtubules.","date":"2012","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/23169647","citation_count":131,"is_preprint":false},{"pmid":"22116939","id":"PMC_22116939","title":"Two-stage genome-wide association study identifies variants in CAMSAP1L1 as susceptibility loci for epilepsy in Chinese.","date":"2011","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/22116939","citation_count":61,"is_preprint":false},{"pmid":"32084403","id":"PMC_32084403","title":"Microtubule Minus-End Binding Protein CAMSAP2 and Kinesin-14 Motor KIFC3 Control Dendritic Microtubule Organization.","date":"2020","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/32084403","citation_count":34,"is_preprint":false},{"pmid":"32206120","id":"PMC_32206120","title":"CAMSAP2-mediated noncentrosomal microtubule acetylation drives hepatocellular carcinoma metastasis.","date":"2020","source":"Theranostics","url":"https://pubmed.ncbi.nlm.nih.gov/32206120","citation_count":30,"is_preprint":false},{"pmid":"35762204","id":"PMC_35762204","title":"CAMSAP2 organizes a γ-tubulin-independent microtubule nucleation centre through phase separation.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/35762204","citation_count":28,"is_preprint":false},{"pmid":"30994903","id":"PMC_30994903","title":"CAMSAP2 Is a Microtubule Minus-End Targeting Protein That Regulates BTB Dynamics Through Cytoskeletal Organization.","date":"2019","source":"Endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/30994903","citation_count":23,"is_preprint":false},{"pmid":"36207462","id":"PMC_36207462","title":"CAMSAP2 promotes colorectal cancer cell migration and invasion through activation of JNK/c-Jun/MMP-1 signaling pathway.","date":"2022","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/36207462","citation_count":21,"is_preprint":false},{"pmid":"28726242","id":"PMC_28726242","title":"Noncentrosomal microtubules regulate autophagosome transport through CAMSAP2-EB1 cross-talk.","date":"2017","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/28726242","citation_count":7,"is_preprint":false},{"pmid":"36718359","id":"PMC_36718359","title":"CAMSAP2 localizes to the Golgi in islet β-cells and facilitates Golgi-ER trafficking.","date":"2023","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/36718359","citation_count":7,"is_preprint":false},{"pmid":"38159595","id":"PMC_38159595","title":"CAMSAP2 enhances lung cancer cell metastasis by mediating RASAL2 degradation.","date":"2023","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/38159595","citation_count":5,"is_preprint":false},{"pmid":"24148305","id":"PMC_24148305","title":"The potential role of CAMSAP1L1 in symptomatic epilepsy.","date":"2013","source":"Neuroscience letters","url":"https://pubmed.ncbi.nlm.nih.gov/24148305","citation_count":5,"is_preprint":false},{"pmid":"37814859","id":"PMC_37814859","title":"[High expression of CAMSAP2 promotes invasion and metastasis of gastric cancer cells by upregulating TGF-β signaling].","date":"2023","source":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","url":"https://pubmed.ncbi.nlm.nih.gov/37814859","citation_count":4,"is_preprint":false},{"pmid":"38839944","id":"PMC_38839944","title":"Deficiency of CAMSAP2 impairs olfaction and the morphogenesis of mitral cells.","date":"2024","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/38839944","citation_count":1,"is_preprint":false},{"pmid":"39787108","id":"PMC_39787108","title":"CAMSAP2 is required for bridging fiber assembly to ensure mitotic spindle assembly and chromosome segregation in human epithelial Caco-2 cells.","date":"2025","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/39787108","citation_count":1,"is_preprint":false},{"pmid":"40333320","id":"PMC_40333320","title":"MARK2 regulates Golgi apparatus reorientation by phosphorylation of CAMSAP2 in directional cell migratio.","date":"2025","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/40333320","citation_count":0,"is_preprint":false},{"pmid":"41620802","id":"PMC_41620802","title":"miR-145-5p/CAMSAP2 axis modulates cisplatin sensitivity in non-small cell lung cancer.","date":"2026","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/41620802","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10859,"output_tokens":3291,"usd":0.040971,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10809,"output_tokens":3155,"usd":0.06646,"stage2_stop_reason":"end_turn"},"total_usd":0.107431,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"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.\",\n      \"method\": \"Live-cell imaging, high-resolution microscopy, laser-based microsurgery, RNAi knockdown in cultured neurons and in vivo\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (live imaging, microsurgery, in vitro and in vivo KD), replicated in the field\",\n      \"pmids\": [\"24908486\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"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.\",\n      \"method\": \"Immunofluorescence, siRNA depletion, organelle distribution analysis in epithelial cells\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal localization, double-depletion epistasis, organelle readout with multiple methods\",\n      \"pmids\": [\"23169647\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"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.\",\n      \"method\": \"In vitro reconstitution assay, phase-separation assay, electron microscopy, fluorescence microscopy\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution with direct biochemical and structural imaging, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"35762204\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"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.\",\n      \"method\": \"Co-immunoprecipitation, RNAi knockdown, live-cell microtubule dynamics imaging in cultured neurons\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP interaction and KD phenotype with dynamics readout, single lab\",\n      \"pmids\": [\"32084403\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"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.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, western blotting, ChIP, luciferase reporter assay, siRNA knockdown, in vivo orthotopic metastasis model\",\n      \"journal\": \"Theranostics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (Co-IP, ChIP, luciferase, in vivo), single lab\",\n      \"pmids\": [\"32206120\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"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.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, live-cell imaging of autophagosome transport in HeLa cells\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP interaction and KD with transport readout, single lab, two orthogonal methods\",\n      \"pmids\": [\"28726242\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"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.\",\n      \"method\": \"Immunofluorescence localization, siRNA knockdown, Golgi-ER trafficking assay, insulin content and secretion measurement in primary β-cells\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization with functional consequence (trafficking, insulin content), multiple readouts, single lab\",\n      \"pmids\": [\"36718359\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"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.\",\n      \"method\": \"Mass spectrometry phospho-mapping, co-immunoprecipitation, mutagenesis, live-cell imaging of Golgi reorientation\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — MS-identified phosphosite, mutagenesis, Co-IP differential binding, functional Golgi readout; single lab\",\n      \"pmids\": [\"40333320\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"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.\",\n      \"method\": \"CAMSAP2 knockout (CRISPR), live-cell imaging of mitosis, spindle morphometry, chromosome segregation analysis\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with multiple defined mitotic phenotypes, live imaging; single lab\",\n      \"pmids\": [\"39787108\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"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).\",\n      \"method\": \"Camsap2 knockout mice, olfactory behavioral assays, morphological analysis of mitral cell dendrites, immunofluorescence\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO mouse with specific behavioral and morphological phenotype readouts; single lab\",\n      \"pmids\": [\"38839944\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"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.\",\n      \"method\": \"siRNA knockdown in SH-SY5Y cells, immunofluorescence co-localization, neurite morphometry\",\n      \"journal\": \"Neuroscience letters\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single KD method with morphometric readout, no pathway mechanism\",\n      \"pmids\": [\"24148305\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"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.\",\n      \"method\": \"Co-immunoprecipitation, proteomic analysis, ubiquitin-proteasome pathway assays, siRNA knockdown, in vivo tail-vein metastasis model\",\n      \"journal\": \"Life sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — Co-IP and biochemical degradation assay in single lab, limited mechanistic validation of the ubiquitin pathway\",\n      \"pmids\": [\"38159595\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"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.\",\n      \"method\": \"siRNA knockdown and overexpression, wound-healing and transwell assays, western blotting for JNK/c-Jun/MMP-1, in vivo lung metastasis model\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — pathway placement by KD/OE phenotype, single lab, no direct binding or enzymatic assay\",\n      \"pmids\": [\"36207462\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CAMSAP2 is a microtubule minus-end binding protein that stabilizes non-centrosomal microtubules by decorating and protecting their minus-ends; it also acts as a γ-tubulin-independent microtubule nucleator through phase separation with αβ-tubulin. In neurons, CAMSAP2 organizes non-centrosomal microtubule arrays to control axon specification, dendritic development, and mitral cell morphogenesis, partly by anchoring the kinesin-14 motor KIFC3 at minus-ends in dendrites. In epithelial cells, CAMSAP2 cooperates with CAMSAP3 to maintain non-centrosomal microtubule networks and suppress centrosomal microtubule growth, and is required for bridging fiber assembly during mitosis. CAMSAP2 anchors microtubules to the Golgi apparatus and its phosphorylation by MARK2 at Ser-835 regulates Golgi reorientation during cell migration by modulating interaction with USO1. In pancreatic β-cells, a distinct CAMSAP2 isoform localizes to the Golgi independently of microtubule binding and promotes Golgi-ER trafficking. Additionally, CAMSAP2 cross-talks with EB1 to regulate microtubule dynamics, autophagosome transport, and cancer cell invasiveness via Trio/Rac1/JNK signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CAMSAP2 is a microtubule minus-end binding protein that organizes and stabilizes non-centrosomal microtubule arrays across diverse cell types [#0, #1]. 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 [#0, #1]. 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 [#2]. In neurons, this minus-end activity establishes neuronal polarity and drives axon specification and dendritic branching [#0], in part by anchoring the kinesin-14 motor KIFC3 at dendritic minus-ends to immobilize microtubules [#3]; in mice, CAMSAP2 loss disrupts mitral cell dendritic remodeling and olfactory circuit formation [#9]. In epithelial cells CAMSAP2 acts together with CAMSAP3 to maintain the non-centrosomal network and proper organelle positioning [#1], and is required specifically for bridging fiber assembly and accurate chromosome segregation during mitosis [#8]. 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 [#7]. A distinct, microtubule-binding-independent isoform localizes to the Golgi in pancreatic β-cells to promote Golgi-to-ER trafficking and insulin production [#6]. CAMSAP2 further cooperates with EB1 to tune microtubule dynamics and retrograde autophagosome transport [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"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.\",\n      \"evidence\": \"Immunofluorescence, siRNA single/double depletion, and organelle distribution analysis in epithelial cells\",\n      \"pmids\": [\"23169647\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve how CAMSAP2 versus CAMSAP3 divide labor at minus-ends\", \"Mechanism of minus-end recognition not defined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"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.\",\n      \"evidence\": \"Live-cell imaging, high-resolution microscopy, laser microsurgery, and RNAi in cultured neurons and in vivo\",\n      \"pmids\": [\"24908486\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify the motors or anchors executing minus-end array organization\", \"Molecular basis of minus-end protection unresolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Connected CAMSAP2 to EB1-dependent microtubule dynamics in a transport context, showing CAMSAP2-EB1 association modulates plus-end growth and retrograde autophagosome transport.\",\n      \"evidence\": \"Co-immunoprecipitation, siRNA knockdown, and live imaging of autophagosome transport in HeLa cells\",\n      \"pmids\": [\"28726242\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct biochemical CAMSAP2-EB1 interaction not structurally characterized\", \"Single lab, two methods\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"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.\",\n      \"evidence\": \"Co-immunoprecipitation, RNAi, and live microtubule dynamics imaging in cultured neurons\",\n      \"pmids\": [\"32084403\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Co-IP without reciprocal/structural validation\", \"Whether anchoring is direct vs. via additional factors unclear\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"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.\",\n      \"evidence\": \"In vitro reconstitution and phase-separation assays with electron and fluorescence microscopy\",\n      \"pmids\": [\"35762204\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo contribution of phase-separation nucleation versus templated stabilization not quantified\", \"Single lab\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"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.\",\n      \"evidence\": \"Immunofluorescence, siRNA knockdown, Golgi-ER trafficking assay, and insulin measurements in primary β-cells\",\n      \"pmids\": [\"36718359\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism of Golgi targeting of this isoform unknown\", \"Trafficking partners at the Golgi not identified\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"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.\",\n      \"evidence\": \"Mass spectrometry phospho-mapping, mutagenesis, Co-IP differential binding, and live imaging of Golgi reorientation\",\n      \"pmids\": [\"40333320\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether USO1 binding is direct not shown structurally\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed a non-redundant mitotic role for CAMSAP2 in bridging fiber assembly and faithful chromosome segregation, distinguishing it from CAMSAP3 in spindle function.\",\n      \"evidence\": \"CRISPR knockout, live-cell mitosis imaging, spindle morphometry, and segregation analysis in Caco-2 cells\",\n      \"pmids\": [\"39787108\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How CAMSAP2 contributes to bridging fiber minus-ends mechanistically unresolved\", \"Single cell line\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"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.\",\n      \"evidence\": \"No single study integrates these activities or provides a structural model\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structure of CAMSAP2 on minus-ends\", \"Relative in vivo contribution of nucleation vs. stabilization unknown\", \"Isoform-specific functional partitioning incompletely mapped\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1, 2, 3]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1, 6, 7]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CAMSAP3\", \"KIFC3\", \"EB1\", \"USO1\", \"MARK2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":8,"faith_pct":87.5}}