Affinage

CHMP2B

Charged multivesicular body protein 2b · UniProt Q9UQN3

Length
213 aa
Mass
23.9 kDa
Annotated
2026-06-09
75 papers in source corpus 27 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CHMP2B is a core ESCRT-III subunit that polymerizes into helical membrane-deforming lattices and underlies endolysosomal, autophagic, and synaptic membrane remodeling, with its dysfunction causing frontotemporal dementia (FTD3) and contributing to ALS (PMID:16041373, PMID:21926173). Purified CHMP2B preferentially binds PI(4,5)P2-containing membranes, assembles into a tightly packed helical coat that rigidifies and tubulates the bilayer, and concentrates at membrane necks where it acts as a diffusion barrier to lipids and membrane proteins (PMID:21926173, PMID:29967034, PMID:33832485). Productive turnover of the polymer requires VPS4-mediated release from membranes (PMID:21926173). FTD3-causative C-terminal truncations (e.g. CHMP2B-Intron5) act through a gain of function: the mutant protein fails to recruit VPS4, becomes stably trapped on endosomal membranes, blocks Rab7 recruitment and thereby endosome-lysosome fusion, impairs autophagic flux, and produces enlarged endolysosomes and neuronal lysosomal storage pathology (PMID:20223751, PMID:20352044, PMID:22366797, PMID:26358247, PMID:30496365). In neurons CHMP2B is part of a stable perisynaptic ESCRT-III complex required for dendritic spine growth, excitatory synapse density, activity-dependent potentiation, and presynaptic vesicle recycling, and its activity-regulated axonal transport to boutons depends on kinesin-binding protein (PMID:20699355, PMID:25698751, PMID:34855215, PMID:40021219). Beyond canonical ESCRT functions, CHMP2B regulates CK1 abundance to control TDP-43 phosphorylation independently of autophagy (PMID:34726688), and sustained CHMP2B activity promotes CHMP7-mediated nuclear pore complex injury in sporadic ALS neurons (PMID:39709457). Disease severity is modulated by physical and genetic interactors including TMEM106B and spastin (PMID:26651479, PMID:36414997), and the C-terminus also encodes a CRM1-dependent nuclear export signal lost upon the FTD3 truncation (PMID:41559796).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2005 High

    Established CHMP2B as a disease gene, linking ESCRT-III dysfunction to neurodegeneration for the first time.

    Evidence Genetic linkage and splice-site mutation analysis in a Danish FTD3 pedigree showing aberrant mRNA splicing in patient tissue

    PMID:16041373

    Open questions at the time
    • Did not define the cellular mechanism of toxicity
    • Did not distinguish loss- vs gain-of-function
  2. 2007 Medium

    Connected C-terminal truncation specifically to endosomal morphological dysfunction.

    Evidence Overexpression of two independent truncation mutants in SK-N-SH neuroblastoma cells with fluorescence microscopy of endosomes

    PMID:17956895

    Open questions at the time
    • Overexpression artifact possible
    • Molecular step disrupted not identified
  3. 2010 High

    Defined where in the endolysosomal pathway mutant CHMP2B acts, identifying Rab7 recruitment failure as the block to endosome-lysosome fusion, and showed disruption of the autophagy-lysosomal pathway.

    Evidence Patient fibroblasts/brain Rab7 localization assays; transfection of mutant CHMP2B in HEK-293/COS-7 with CD63 and LC3-II readouts

    PMID:20223751 PMID:20352044

    Open questions at the time
    • Did not show how mutant remains membrane-bound
    • MVB sorting itself intact
  4. 2012 High

    Distinguished gain-of-function from loss-of-function, establishing that the truncation mutant, not loss of CHMP2B, drives neurodegeneration.

    Evidence Comparative transgenic (mutant vs WT) and Chmp2b knockout mice with neuropathological analysis

    PMID:22366797

    Open questions at the time
    • Did not define the molecular trapping mechanism
    • Cell-type selectivity unexplained
  5. 2011 High

    Provided the structural basis for CHMP2B function, showing it forms a VPS4-dependent helical membrane-deforming polymer.

    Evidence Cryo-EM of CHMP2B membrane tubes plus VPS4 depletion and CHMP4 relocalization in cells

    PMID:21926173

    Open questions at the time
    • Physiological membrane target not defined
    • Lipid specificity not yet measured
  6. 2012 Medium

    Placed CHMP2B-linked autophagy defects in a maturation pathway via genetic modifiers and probed ESCRT dissociation defects of a missense mutant.

    Evidence Drosophila modifier screen identifying STX13/Vti1a; missense T104N Co-IP with VPS4/Snf7-2 and EGFR degradation assays in neurons

    PMID:22521643 PMID:24095276

    Open questions at the time
    • STX13-CHMP2B physical link not shown
    • T104N Co-IP single lab without reciprocal validation
  7. 2010 High

    Identified a physiological synaptic role for CHMP2B in spine growth and excitatory transmission, with mutants acting dominant-negatively.

    Evidence Mutant expression and RNAi in hippocampal neurons with spine morphometry and mEPSC recordings

    PMID:20699355

    Open questions at the time
    • Molecular mechanism at spines not defined
    • Relation to ESCRT membrane activity unclear
  8. 2015 High

    Defined CHMP2B as part of a stable perisynaptic ESCRT-III complex required for synapse formation and plasticity in vivo, and identified lysosomal storage as the major neuronal pathology.

    Evidence Immuno-EM, CoIP-MS, depletion phenotypes in vitro/in vivo; physiological-level transgenic mice with ultrastructure and patient brain confirmation

    PMID:25698751 PMID:26358247

    Open questions at the time
    • Composition of synaptic complex only partially resolved
    • Link between storage pathology and synaptic loss unresolved
  9. 2015 Medium

    Identified TMEM106B as a physical and functional modifier of CHMP2B toxicity in the endolysosomal pathway.

    Evidence Co-IP of TMEM106B risk variants with CHMP2B plus EGFR/autophagy/viability assays in overexpression

    PMID:26651479

    Open questions at the time
    • Overexpression system
    • Direct vs indirect interaction not resolved
  10. 2017 High

    Demonstrated mitochondrial and endosomal dysfunction in patient neurons attributable to the mutation using isogenic correction.

    Evidence FTD3 patient iPSC cortical neurons with CRISPR isogenic controls; EM, respirometry, ROS and iron assays

    PMID:28216144

    Open questions at the time
    • Mechanistic link between ESCRT defect and mitochondrial phenotype unclear
    • Iron homeostasis pathway not detailed
  11. 2018 High

    Identified the proximate molecular defect: mutant CHMP2B cannot recruit VPS4, becoming stably trapped and immobilizing dendritic endolysosomes, with TMEM106B knockdown providing rescue.

    Evidence Physiological-level transgenic mice, dendritic endolysosome live imaging, VPS4 recruitment assays, TMEM106B ASO rescue

    PMID:30496365

    Open questions at the time
    • How truncation abolishes VPS4 recruitment structurally not shown
    • Whether trafficking arrest fully accounts for degeneration unknown
  12. 2018 High

    Defined CHMP2B's membrane biophysics: PI(4,5)P2 preference and diffusion-barrier function at membrane necks.

    Evidence Reconstituted GUV-nanotube system with purified CHMP2B and lipid diffusion assays

    PMID:29967034

    Open questions at the time
    • In vivo relevance of barrier function not established
    • Relationship to scission unresolved
  13. 2021 High

    Distinguished CHMP2B from CHMP2A biophysically, showing CHMP2B uniquely binds PI(4,5)P2 and rigidifies membranes without requiring CHMP3.

    Evidence Purified recombinant proteins on biomimetic membranes; biolayer interferometry and membrane mechanics

    PMID:33832485

    Open questions at the time
    • Functional consequence of isoform divergence in cells unresolved
  14. 2021 High

    Revealed an autophagy-independent role: CHMP2B controls CK1 abundance via ubiquitin-proteasome turnover to modulate TDP-43 phosphorylation and toxicity.

    Evidence Drosophila and mammalian cell knockdown/overexpression; CK1 inhibition, ubiquitination and proteasome assays

    PMID:34726688

    Open questions at the time
    • Direct CHMP2B-CK1 interaction not defined
    • Connection to ESCRT activity unclear
  15. 2021 Medium

    Characterized CHMP2B-FTD as a synaptopathy involving presynaptic vesicle recycling defects, and identified spastin as a mutation-enhanced binding partner.

    Evidence Aged transgenic mice with synaptic marker IHC, EM and SV recycling assays; Co-IP, fractionation and Drosophila epistasis for spastin

    PMID:34855215 PMID:36414997

    Open questions at the time
    • Causal chain from sequestration to synaptic failure incomplete
    • Spastin interaction single lab
  16. 2024 Medium

    Extended CHMP2B's pathological reach to nuclear pore injury in sporadic ALS, where sustained CHMP2B activation drives CHMP7 accumulation and TDP-43 dysfunction.

    Evidence sALS iPSC neurons with partial CHMP2B knockdown, super-resolution microscopy and NPC composition analysis

    PMID:39709457

    Open questions at the time
    • Mechanism of CHMP2B 'activation' undefined
    • Single lab iPSC model
  17. 2025 Medium

    Showed activity-dependent axonal transport of CHMP2B to presynaptic boutons depends on kinesin-binding protein, with the FTD mutant failing transport.

    Evidence Live imaging of CHMP2B axonal trafficking with KBP binding assays comparing WT vs Intron5

    PMID:40021219

    Open questions at the time
    • KBP-CHMP2B binding interface not mapped
    • Single lab
  18. 2026 Medium

    Identified a C-terminal CRM1-dependent nuclear export signal lost in the FTD3 mutant, causing nuclear mislocalization.

    Evidence iPSC cortical neurons with leptomycin B and NES site-directed mutagenesis; localization and export assays

    PMID:41559796

    Open questions at the time
    • Functional consequence of nuclear CHMP2B unresolved
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse downstream consequences of mutant CHMP2B (endolysosomal arrest, mitochondrial dysfunction, NPC injury, CK1/TDP-43 regulation, nuclear mislocalization) are mechanistically unified and which drive neurodegeneration remains unresolved.
  • No unified model linking membrane-trapping to nuclear and mitochondrial phenotypes
  • Therapeutic node for FTD3/ALS not validated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0008289 lipid binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005768 endosome 3 GO:0005764 lysosome 2 GO:0005886 plasma membrane 2 GO:0005634 nucleus 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9612973 Autophagy 2
Partners
CHMP4BCHMP7KBPSPASTINSTX13TMEM106BVPS4
Complex memberships
ESCRT-III

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 CHMP2B is a component of the endosomal ESCRT-III complex; a splice-site mutation causes aberrant mRNA splicing and is causative for frontotemporal dementia (FTD3) in a Danish pedigree, implicating ESCRT-III dysfunction in neurodegeneration. Genetic linkage, mutation identification, mRNA splicing analysis in patient tissue Nature genetics High 16041373
2007 C-truncating mutations in CHMP2B (both Danish p.Met178ValfsX2 and Belgian p.Gln165X) cause formation of large, aberrant endosomal structures when overexpressed in human neuroblastoma SK-N-SH cells, linking C-terminal truncation to endosomal dysfunction. Overexpression of mutant CHMP2B constructs in SK-N-SH cells, fluorescence microscopy of endosomal morphology Human molecular genetics Medium 17956895
2010 Mutant CHMP2B disrupts endosome-lysosome fusion but not protein sorting by the MVB. The mechanism involves mutant CHMP2B constitutively binding to MVBs and preventing recruitment of Rab7, a protein necessary for endosome-lysosome fusion. Functional assays in patient fibroblasts and patient brain tissue; Rab7 localization studies; endosomal morphology analysis Human molecular genetics High 20223751
2010 Transfection of mutant CHMP2B into HEK-293 and COS-7 cells results in large cytoplasmic vacuoles, aberrant lysosomal localization (CD63 staining), and impairment of autophagy (increased LC3-II), demonstrating that CHMP2B mutations disrupt the autophagy-lysosomal pathway. Transfection of mutant vs. wild-type CHMP2B in HEK-293 and COS-7 cells; CD63 immunostaining; LC3-II western blot PloS one Medium 20352044
2010 CHMP2B is required for normal dendritic spine growth. FTD-linked CHMP2B mutants (CHMP2B-Intron5 and CHMP2B-Delta10) reduce the proportion of large mushroom-shaped spines in hippocampal neurons; CHMP2B-Delta10 also reduces frequency and amplitude of excitatory postsynaptic currents. RNAi depletion of endogenous CHMP2B phenocopies mutants, indicating dominant-negative activity. Expression of mutant CHMP2B in cultured hippocampal neurons; confocal microscopy and 3D reconstruction of spine morphology; electrophysiology (mEPSC recordings); RNAi knockdown Journal of cell science High 20699355
2011 CHMP2B polymerizes into helical structures that deform membranes in cellulo. Depletion of VPS4 induces accumulation of endogenous CHMP2B at the plasma membrane; overexpressed full-length CHMP2B forms long, rigid tubes protruding from cells. Cryo-EM shows CHMP2B polymerizes into a tightly packed helical lattice closely associated with the inner leaflet of membrane tubes, sufficient to deform the lipid bilayer. CHMP4s relocalize at the base of the tubes; tube formation depends on VPS4. VPS4 depletion; live-cell imaging; cryo-electron microscopy of CHMP2B membrane tubes; immunofluorescence of CHMP4 localization The Journal of biological chemistry High 21926173
2012 Transgenic mice expressing C-terminally truncated mutant CHMP2B show progressive neurodegeneration (gliosis, p62/ubiquitin-positive inclusions, axonal swellings) not seen in Chmp2b knockout or wild-type CHMP2B transgenic mice, establishing that CHMP2B mutations cause neurodegeneration via a gain-of-function mechanism. Transgenic mouse models (mutant CHMP2B, wild-type CHMP2B, Chmp2b knockout); immunohistochemistry; neuropathological analysis Brain : a journal of neurology High 22366797
2012 STX13 (syntaxin 13) is a genetic modifier of mutant CHMP2B and is required for autophagosome maturation. Knockdown of STX13 or its binding partner Vti1a in mammalian cells causes accumulation of LC3-positive puncta and blocks autophagic flux. STX13 is present on LC3-positive phagophores and multilamellar structures induced by dysfunctional ESCRT-III. Loss of STX13 causes accumulation of Atg5-positive puncta and multilamellar structure formation, indicating STX13 participates in phagophore-to-autophagosome maturation. Drosophila genetic modifier screen with mutant CHMP2B; mammalian cell knockdown of STX13 and Vti1a; LC3/Atg5 immunofluorescence; autophagic flux assays Molecular cell High 24095276
2012 CHMP2B missense mutant T104N accumulates in Rab5- and Rab7-positive endosomes, causes delayed EGFR degradation, shows reduced association with Vps4 ATPase and increased association with Snf7-2 (ESCRT-III core component), and causes autophagosome accumulation in post-mitotic neurons — indicating defects in ESCRT dissociation from endosomes. Transfection of missense mutant CHMP2B in post-mitotic neurons; Rab5/Rab7 co-localization; EGFR degradation assay; Co-immunoprecipitation with Vps4 and Snf7-2; LC3 autophagosome accumulation assay Biochemical and biophysical research communications Medium 22521643
2013 Expression of CHMP2B-Intron5 in Drosophila causes accumulation of Notch in enlarged endosomes and upregulation of Notch signaling activity; partial loss of Notch activity rescues eye deformities and behavioral defects, demonstrating that mutant CHMP2B disrupts Notch receptor trafficking and signaling. Drosophila genetics (eyeless-Gal4 driver); Notch immunofluorescence; epistasis with Notch loss-of-function; phototactic behavior assay FASEB journal Medium 24158394
2015 Neuronal Chmp2b concentrates beneath the perisynaptic membrane of dendritic spines (by quantitative immuno-EM). Depletion of endogenous Chmp2b reduces dendritic branching, decreases excitatory synapse density in vitro and in vivo, and abolishes activity-induced spine enlargement and synaptic potentiation. Co-immunoprecipitation and mass spectrometry show Chmp2b is part of a stable complex containing other Chmp family members and postsynaptic scaffolds, corresponding to a stable ESCRT-III form at synapses. Quantitative immuno-electron microscopy; Chmp2b depletion (in vitro and in vivo); synaptic plasticity assays; co-immunoprecipitation + mass spectrometry The Journal of neuroscience High 25698751
2015 Mice expressing FTD-causative mutant CHMP2B at physiological levels develop lysosomal storage pathology characterized by large neuronal autofluorescent aggregates derived from the endolysosomal system (confirmed by ultrastructural analysis and immuno-gold labeling), not seen in wild-type CHMP2B mice. Similar aggregates are found in CHMP2B patient brains, identifying lysosomal storage pathology as the major neuronal pathology in CHMP2B-FTD. Transgenic mice at physiological expression levels; autofluorescence imaging; ultrastructural analysis (EM); immuno-gold labeling; human patient brain analysis Acta neuropathologica High 26358247
2015 TMEM106B (T185 risk variant) associates more strongly with CHMP2B than S185 variant by co-immunoprecipitation, and is more localized to Rab7-positive endosomes. T185 enhances EGFR accumulation, autophagic flux impairment, and neurotoxicity caused by CHMP2B-Intron5, suggesting functional interaction between TMEM106B and CHMP2B in the ESCRT/endolysosomal pathway. Co-immunoprecipitation of TMEM106B variants with CHMP2B; Rab5/Rab7 localization; EGFR degradation assay; autophagy flux assay; cell viability Molecular brain Medium 26651479
2017 FTD3 patient iPSC-derived cortical neurons show abnormal endosomes, defective mitochondrial cristae formation, reduced mitochondrial respiration, increased reactive oxygen species, and perturbed iron homeostasis. All phenotypes are rescued in CRISPR/Cas9-corrected isogenic controls, directly linking mutant CHMP2B to mitochondrial and endosomal dysfunction in human neurons. Patient iPSC differentiation into cortical neurons; CRISPR/Cas9 isogenic correction; electron microscopy of mitochondria; Seahorse respirometry; ROS measurement; iron homeostasis assays Stem cell reports High 28216144
2018 Physiological levels of mutant CHMP2B cause stable incorporation onto neuronal endolysosomes, rendering them unable to traffic within dendrites. This defect is due to inability of mutant CHMP2B to recruit VPS4, which is required for CHMP2B release from endosomal membranes. Antisense oligonucleotides targeting TMEM106B rescue both impaired endolysosomal trafficking and increased dendritic branching. Transgenic mice at physiological expression levels; live imaging of endolysosomal trafficking in dendrites; VPS4 recruitment assay; ASO treatment and rescue Brain : a journal of neurology High 30496365
2018 CHMP2B preferentially binds to membranes containing PI(4,5)P2 (phosphatidylinositol 4,5-bisphosphate). CHMP2B (both full-length and C-terminal deletion ΔC) preferentially accumulates at the neck of membrane nanotubes and prevents diffusion of PI(4,5)P2 lipids and membrane-bound proteins across the tube neck, functioning as a diffusion barrier at membrane necks. Reconstituted GUV-nanotube system; purified CHMP2B protein; lipid diffusion assay; fluorescence microscopy Journal of cell science High 29967034
2009 In a Drosophila model of FTD3, a genome-wide genetic screen identified Serpin5 (Spn5) as a suppressor of mutant CHMP2B toxicity. Spn5 is a negative regulator of the Toll pathway, functioning extracellularly by blocking proteolytic activation of Spaetzle (Toll receptor ligand). Spn5 inhibited Toll pathway activation by mutant CHMP2B, identifying the Toll pathway as a major signaling pathway misregulated by mutant CHMP2B in vivo. Drosophila model expressing CHMP2B-Intron5; genome-wide genetic modifier screen; epistasis analysis with Toll pathway components Proceedings of the National Academy of Sciences of the United States of America Medium 19581577
2021 CHMP2B downregulation reduces TDP-43 phosphorylation and toxicity in flies and mammalian cells independently of autophagy. Inhibition of CK1 (casein kinase 1) abolishes CHMP2B's modifying effect on TDP-43 phosphorylation. CHMP2B modulates CK1 protein levels by negatively regulating ubiquitination and proteasome-mediated turnover of CK1, revealing an autophagy-independent role for CHMP2B in regulating CK1 abundance. Drosophila genetic screen; mammalian cell knockdown/overexpression; TDP-43 phosphorylation assays; CK1 inhibitor treatment; ubiquitination assay; proteasome inhibition experiment The Journal of cell biology High 34726688
2021 CHMP2B binding is enhanced in the presence of PI(4,5)P2 lipids, whereas CHMP2A does not display lipid specificity and requires CHMP3 for membrane binding. CHMP2B forms a reticular membrane structure and strongly rigidifies membranes upon polymerization; CHMP2A (+CHMP3) binds homogeneously and has no significant effect on membrane rigidity, demonstrating distinct biophysical properties of the two CHMP2 isoforms. Purified recombinant proteins; biomimetic membrane systems (GUVs, lipid bilayers); biolayer interferometry; membrane mechanics measurements; fluorescence microscopy BMC biology High 33832485
2021 Expression of C-terminally truncated mutant CHMP2B in mice causes selective retention of presynaptic SV (synaptic vesicle) trafficking proteins with significant loss of postsynaptic proteins. Ultrastructural analysis reveals increased presynaptic endosomes; neurons expressing mutant CHMP2B display defective SV recycling and altered functional SV pools, identifying CHMP2B FTD as a novel synaptopathy. Aged mutant CHMP2B transgenic mice; immunohistochemistry for pre- and postsynaptic markers; electron microscopy; SV recycling assays in primary cortical cultures Journal of neurochemistry Medium 34855215
2022 SIRT6 negatively regulates CHMP2B accumulation in aged hearts. SIRT6 decreases acetylation of FoxO1, promoting its transcriptional function on Atrogin-1 (a muscle-specific E3 ubiquitin ligase), which subsequently enhances proteasomal degradation of CHMP2B. CHMP2B accumulation in aged hearts impairs autophagic flux, worsening myocardial ischemia-reperfusion injury. Myocardial-specific SIRT6 heterozygous knockout mice; SIRT6 activation pharmacology; FoxO1 acetylation assays; Atrogin-1 transcription assays; ubiquitination of CHMP2B; autophagic flux measurement Journal of cardiovascular translational research Medium 35235147
2022 Mutant CHMP2B-Intron5 binds spastin with greater affinity than wild-type CHMP2B, and colocalizes with CHMP2B-Intron5 in p62-positive aggregates. In cells expressing CHMP2B-Intron5, cytoplasmic soluble spastin decreases while insoluble spastin increases. Genetic knockdown of spastin enhances CHMP2B-Intron5 toxicity in Drosophila, demonstrating functional interaction. Co-immunoprecipitation; immunofluorescence co-localization; soluble/insoluble fractionation; Drosophila genetic epistasis (spastin knockdown) Acta neuropathologica communications Medium 36414997
2024 CHMP2B promotes CHMP7-mediated nuclear pore complex (NPC) injury in sporadic ALS iPSC-derived neurons. CHMP2B-dependent sustained 'activation' contributes to pathologic CHMP7 nuclear accumulation and POM121 reduction at NPCs. Partial knockdown of CHMP2B alleviates NPC injury and downstream TDP-43 dysfunction in sALS neurons. iPSC-derived neurons from sALS patients; partial CHMP2B knockdown; super-resolution microscopy; NPC composition analysis (POM121); TDP-43 localization Acta neuropathologica communications Medium 39709457
2025 CHMP2B axonal transport and recruitment to presynaptic boutons are regulated by neuronal activity and depend on kinesin-binding protein (KBP). The FTD-causative CHMP2B-Intron5 mutant shows little processive movement or presynaptic localization; its transport vesicles exhibit oscillatory (tug-of-war) behavior due to deficient binding to kinesin-binding protein, which normally regulates CHMP2B transport. Live imaging of CHMP2B axonal trafficking in neurons; neuronal activity manipulation; KBP binding assays; comparison of WT vs. CHMP2B-Intron5 transport dynamics Life science alliance Medium 40021219
2026 Wild-type CHMP2B contains a nuclear export signal (NES) in its C-terminus that is necessary and sufficient for CRM1-dependent nuclear export. The FTD3-causative CHMP2B-Intron5 mutation removes this NES, causing mislocalization of CHMP2B to the nucleus of iPSC-derived cortical neurons. Site-directed mutagenesis of key hydrophobic NES residues confirms the NES is required for nuclear export. iPSC-derived cortical neurons; CRM1 inhibition (leptomycin B); site-directed mutagenesis of NES residues; immunofluorescence localization; functional export assays Acta neuropathologica communications Medium 41559796
2023 CHMP2B with the T104N (FTD/ALS7-associated) mutation accumulates preferentially in the Golgi body rather than ESCRT-III structures, activates Arf4-mediated Golgi stress signaling, and inhibits neuronal process elongation. Knockdown of Arf4 recovers the neuronal process elongation inhibited by the T104N mutation. N1E-115 neuronal cell line differentiation; immunofluorescence of CHMP2B T104N localization; Arf4 pathway analysis; Arf4 siRNA knockdown rescue Neurology international Medium 37606396
2020 Partial loss of function of Ik2 (fly TBK1 homologue) enhances CHMP2B-Intron5 toxicity in fly eye, while Ik2 overexpression suppresses it. Loss of Spn-F (downstream Ik2 phosphorylation target) also enhances CHMP2B-Intron5 toxicity. Interactome analysis identified a network including Spn-F, Ik2, dynein light chain, and Hook (early endosome transport adaptor). Partial loss of dynein light chain or Hook enhances mutant CHMP2B toxicity, implicating early endosome transport as a contributing pathway. Drosophila genetic epistasis; Ik2/Spn-F loss-of-function and overexpression; protein interactome analysis; Hook and dynein light chain loss-of-function Scientific reports Medium 32848189
2024 CHMP2B and CHMP4B are recruited to Leishmania donovani parasitophorous vacuoles (LdLPVs) together with VPS4a and TSG101, demonstrating CHMP2B participates in ESCRT-III assembly at pathological membrane compartments beyond its canonical endosomal role. Immunofluorescence of ESCRT components at LdLPVs in infected macrophages; dominant-negative VPS4a expression bioRxivpreprint Low
2024 CHMP2B acts after Annexin-mediated membrane sealing in a sequential 'sealing and healing' membrane repair pathway. FTD- and ALS-associated mutations in CHMP2B compromise the repair process (ESCRT-III-mediated shedding of damaged membranes). Temporal recruitment analysis of ESCRT-III and Annexins to membrane damage sites; CHMP2B mutant functional analysis in membrane repair assay bioRxivpreprint Low
2025 In CHMP2A knockout cells, CHMP2B localization at the abscission site is minimally disrupted during cytokinesis, whereas CHMP4B, CHMP3, and CHMP1B show progressively severe organization defects, indicating CHMP2B is relatively independent of CHMP2A for cytokinetic abscission site targeting. CHMP2A knockout; live cell imaging; structured illumination microscopy (SIM); correlative light-electron microscopy (CLEM) bioRxivpreprint Low

Source papers

Stage 0 corpus · 75 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nature genetics 674 16041373
2006 ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B). Neurology 322 16807408
2010 Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS). PloS one 192 20352044
2010 Disruption of endocytic trafficking in frontotemporal dementia with CHMP2B mutations. Human molecular genetics 148 20223751
2007 CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro. Human molecular genetics 128 17956895
2012 Progressive neuronal inclusion formation and axonal degeneration in CHMP2B mutant transgenic mice. Brain : a journal of neurology 89 22366797
2011 Charged multivesicular body protein 2B (CHMP2B) of the endosomal sorting complex required for transport-III (ESCRT-III) polymerizes into helical structures deforming the plasma membrane. The Journal of biological chemistry 88 21926173
2015 Frontotemporal dementia caused by CHMP2B mutation is characterised by neuronal lysosomal storage pathology. Acta neuropathologica 81 26358247
2011 Frontotemporal dementia caused by CHMP2B mutations. Current Alzheimer research 75 21222599
2009 Genetic screen identifies serpin5 as a regulator of the toll pathway and CHMP2B toxicity associated with frontotemporal dementia. Proceedings of the National Academy of Sciences of the United States of America 70 19581577
2017 Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B. Stem cell reports 66 28216144
2013 Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is required for autophagosome maturation. Molecular cell 61 24095276
2010 CHMP2B mutants linked to frontotemporal dementia impair maturation of dendritic spines. Journal of cell science 60 20699355
2010 Immunopositivity for ESCRT-III subunit CHMP2B in granulovacuolar degeneration of neurons in the Alzheimer's disease hippocampus. Neuroscience letters 51 20420883
2009 The role of CHMP2B in frontotemporal dementia. Biochemical Society transactions 51 19143633
2015 Regulation of postsynaptic function by the dementia-related ESCRT-III subunit CHMP2B. The Journal of neuroscience : the official journal of the Society for Neuroscience 49 25698751
2006 CHMP2B mutations are not a common cause of frontotemporal lobar degeneration. Neuroscience letters 49 16431024
2006 Genetic variability in CHMP2B and frontotemporal dementia. Neuro-degenerative diseases 44 16954699
2020 Lessons learned from CHMP2B, implications for frontotemporal dementia and amyotrophic lateral sclerosis. Neurobiology of disease 41 33144171
2016 The role of CHMP2BIntron5 in autophagy and frontotemporal dementia. Brain research 36 26972529
2018 Frontotemporal dementia causative CHMP2B impairs neuronal endolysosomal traffic-rescue by TMEM106B knockdown. Brain : a journal of neurology 35 30496365
2015 TMEM106B, a frontotemporal lobar dementia (FTLD) modifier, associates with FTD-3-linked CHMP2B, a complex of ESCRT-III. Molecular brain 35 26651479
2006 CHMP2B mutations are not a cause of dementia in Dutch patients with familial and sporadic frontotemporal dementia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 32 16941655
2021 The ESCRT-III isoforms CHMP2A and CHMP2B display different effects on membranes upon polymerization. BMC biology 30 33832485
2018 The ESCRT protein CHMP2B acts as a diffusion barrier on reconstituted membrane necks. Journal of cell science 29 29967034
2012 The functional analysis of the CHMP2B missense mutation associated with neurodegenerative diseases in the endo-lysosomal pathway. Biochemical and biophysical research communications 27 22521643
2017 Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation. Human molecular genetics 25 28093491
2022 SIRT6 Protects Against Myocardial Ischemia-Reperfusion Injury by Attenuating Aging-Related CHMP2B Accumulation. Journal of cardiovascular translational research 23 35235147
2012 Endosomal sorting related protein CHMP2B is localized in Lewy bodies and glial cytoplasmic inclusions in α-synucleinopathy. Neuroscience letters 23 22947304
2008 Cortical volumes and atrophy rates in FTD-3 CHMP2B mutation carriers and related non-carriers. NeuroImage 23 19150504
2021 CHMP2B regulates TDP-43 phosphorylation and cytotoxicity independent of autophagy via CK1. The Journal of cell biology 22 34726688
2020 Neuroprotective activity of ursodeoxycholic acid in CHMP2BIntron5 models of frontotemporal dementia. Neurobiology of disease 22 32801000
2010 CHMP2B mutations are rare in French families with frontotemporal lobar degeneration. Journal of neurology 20 20625756
2021 The ESCRT-III protein VPS4, but not CHMP4B or CHMP2B, is pathologically increased in familial and sporadic ALS neuronal nuclei. Acta neuropathologica communications 18 34281622
2012 Cognitive impairment in the preclinical stage of dementia in FTD-3 CHMP2B mutation carriers: a longitudinal prospective study. Journal of neurology, neurosurgery, and psychiatry 18 23142962
2009 Presymptomatic generalized brain atrophy in frontotemporal dementia caused by CHMP2B mutation. Dementia and geriatric cognitive disorders 18 19202337
2010 Mutations in CHMP2B are not a cause of frontotemporal lobar degeneration in Finnish patients. European journal of neurology 16 20412296
2018 Effect of tau-pathology on charged multivesicular body protein 2b (CHMP2B). Brain research 15 30414727
2012 Localization of CHMP2B-immunoreactivity in the brainstem of Lewy body disease. Neuropathology : official journal of the Japanese Society of Neuropathology 15 22989140
2018 Inflammatory markers of CHMP2B-mediated frontotemporal dementia. Journal of neuroimmunology 14 30193769
2012 Presymptomatic cerebral blood flow changes in CHMP2B mutation carriers of familial frontotemporal dementia (FTD-3), measured with MRI. BMJ open 13 22422914
2006 Sequence analysis of all identified open reading frames on the frontal temporal dementia haplotype on chromosome 3 fails to identify unique coding variants except in CHMP2B. Neuroscience letters 13 17095158
2020 Ik2/TBK1 and Hook/Dynein, an adaptor complex for early endosome transport, are genetic modifiers of FTD-associated mutant CHMP2B toxicity in Drosophila. Scientific reports 12 32848189
2012 Reversal of pathology in CHMP2B-mediated frontotemporal dementia patient cells using RNA interference. The journal of gene medicine 12 22786763
2014 Immunohistochemical analysis of expressions of RB1, CDK4, HSP90, cPLA2G4A, and CHMP2B is helpful in distinction between myxofibrosarcoma and myxoid liposarcoma. International journal of surgical pathology 11 24788530
2011 Homozygous microdeletion of the POU1F1, CHMP2B, and VGLL3 genes in chromosome 3--a novel syndrome. American journal of medical genetics. Part A 11 21815258
2021 A novel synaptopathy-defective synaptic vesicle protein trafficking in the mutant CHMP2B mouse model of frontotemporal dementia. Journal of neurochemistry 10 34855215
2017 CSF neurofilament light concentration is increased in presymptomatic CHMP2B mutation carriers. Neurology 10 29237796
2021 Serum Neurofilament Light in Patients with Frontotemporal Dementia Caused by CHMP2B Mutation. Dementia and geriatric cognitive disorders 9 33626531
2013 Expression of mutant CHMP2B, an ESCRT-III component involved in frontotemporal dementia, causes eye deformities due to Notch misregulation in Drosophila. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 24158394
2024 CHMP2B promotes CHMP7 mediated nuclear pore complex injury in sporadic ALS. Acta neuropathologica communications 8 39709457
2019 Expression of mutant CHMP2B linked to neurodegeneration in humans disrupts circadian rhythms in Drosophila. FASEB bioAdvances 7 32123847
2017 TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3). Neurobiology of aging 7 28888721
2022 Six generations of CHMP2B-mediated Frontotemporal Dementia: Clinical features, predictive testing, progression, and survival. Acta neurologica Scandinavica 6 34997757
2022 Alteration of the Neuromuscular Junction and Modifications of Muscle Metabolism in Response to Neuron-Restricted Expression of the CHMP2Bintron5 Mutant in a Mouse Model of ALS-FTD Syndrome. Biomolecules 6 35454086
2023 Endo-lysosomal protein concentrations in CSF from patients with frontotemporal dementia caused by CHMP2B mutation. Alzheimer's & dementia (Amsterdam, Netherlands) 5 36815874
2023 FTD/ALS Type 7-Associated Thr104Asn Mutation of CHMP2B Blunts Neuronal Process Elongation, and Is Recovered by Knockdown of Arf4, the Golgi Stress Regulator. Neurology international 5 37606396
2019 Expression of a human variant of CHMP2B linked to neurodegeneration in Drosophila external sensory organs leads to cell fate transformations associated with increased Notch activity. Developmental neurobiology 5 31587468
2012 Population-specific regulation of Chmp2b by Lbx1 during onset of synaptogenesis in lateral association interneurons. PloS one 5 23284619
2023 A novel splice-site mutation in CHMP2B associated with frontotemporal dementia: The first report from China and literature review. Molecular genetics & genomic medicine 4 37272767
2022 The enhanced association between mutant CHMP2B and spastin is a novel pathological link between frontotemporal dementia and hereditary spastic paraplegias. Acta neuropathologica communications 4 36414997
2021 Cortical Frontoparietal Network Dysfunction in CHMP2B-Frontotemporal Dementia. Frontiers in aging neuroscience 4 34588974
2016 Generation of a human induced pluripotent stem cell line via CRISPR-Cas9 mediated integration of a site-specific homozygous mutation in CHMP2B. Stem cell research 4 27558614
2019 Longitudinal transcriptomic analysis of altered pathways in a CHMP2Bintron5-based model of ALS-FTD. Neurobiology of disease 3 31837425
2016 Generation of a human induced pluripotent stem cell line via CRISPR-Cas9 mediated integration of a site-specific heterozygous mutation in CHMP2B. Stem cell research 3 27558613
2025 Truncation mutation of CHMP2B disrupts late endosome function but reduces TDP-43 aggregation through HSP70 upregulation. Neurochemistry international 2 40316175
2021 Differential levels of CHMP2B, LLPH, and SLC25A51 proteins in secondary renal amyloidosis. Expert review of proteomics 2 33583303
2018 Localization of CHMP2B in postnatal rd1 mouse retina. Bios 1 31281183
2026 Mislocalization of FTD3-associated mutant CHMP2B to the nucleus of human neurons due to loss of a nuclear export signal. Acta neuropathologica communications 0 41559796
2026 CHMP2B exacerbates renal tubular injury in sepsis-induced acute kidney injury by enhancing autophagy blockade. International immunopharmacology 0 42143939
2026 CHMP2B p.Ala30Ser Variant in Biomarker-Confirmed Early-Onset Alzheimer Disease: A Potential Endolysosomal Disease Modifier. Alzheimer disease and associated disorders 0 42246690
2025 Overexpression of CHMP2B suppresses proliferation of renal clear cell carcinoma cells. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 39819721
2025 Axonal transport of CHMP2b is regulated by kinesin-binding protein and disrupted by CHMP2bintron5. Life science alliance 0 40021219
2025 A Novel CHMP2B Splicing Variant in Atypical Presentation of Familial Frontotemporal Lobar Degeneration. Annals of clinical and translational neurology 0 40244880
2024 Modulating Golgi Stress Signaling Ameliorates Cell Morphological Phenotypes Induced by CHMP2B with Frontotemporal Dementia-Associated p.Asp148Tyr. Current issues in molecular biology 0 38392208

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