Affinage

CHMP2B

Charged multivesicular body protein 2b · UniProt Q9UQN3

Length
213 aa
Mass
23.9 kDa
Annotated
2026-04-28
73 papers in source corpus 27 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CHMP2B is a subunit of the ESCRT-III complex that polymerizes into helical filaments on PI(4,5)P2-enriched membranes, forming a diffusion barrier at membrane necks and rigidifying the lipid bilayer; its disassembly requires recruitment of the VPS4 ATPase via the CHMP2B C-terminus (PMID:21926173, PMID:29967034, PMID:33832485). CHMP2B functions in endosome-lysosome fusion, multivesicular body biogenesis, autophagic flux, synaptic vesicle recycling, dendritic spine maturation, and nuclear pore complex homeostasis, and it regulates CK1-dependent TDP-43 phosphorylation independently of autophagy (PMID:20223751, PMID:25698751, PMID:34726688, PMID:39709457). Its C-terminus also harbors a CRM1-dependent nuclear export signal whose loss in the FTD3-causative CHMP2BIntron5 truncation mutant causes nuclear mislocalization; C-terminal truncation mutations lock CHMP2B onto endolysosomal membranes by abolishing VPS4 recruitment, producing gain-of-function endolysosomal trafficking failure, lysosomal storage pathology, and progressive neurodegeneration (PMID:16041373, PMID:30496365, PMID:41559796, PMID:22366797). Mutations in CHMP2B cause chromosome 3-linked frontotemporal dementia (FTD3) and have been implicated in ALS-associated nuclear pore complex injury (PMID:16041373, PMID:39709457).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2005 High

    Identification of CHMP2B as an ESCRT-III subunit whose C-terminal truncation through aberrant splicing causes frontotemporal dementia established the first link between ESCRT-III dysfunction and neurodegeneration.

    Evidence Genetic mapping and mRNA splicing analysis in FTD3 patient tissue

    PMID:16041373

    Open questions at the time
    • Mechanism by which C-terminal truncation disrupts ESCRT-III function was unknown
    • Whether phenotype is loss-of-function or gain-of-function was unresolved
  2. 2007 High

    Demonstrating that C-terminally truncated CHMP2B mutants cause large aberrant endosomal structures upon overexpression established a dominant-negative or gain-of-function cellular mechanism rather than simple haploinsufficiency.

    Evidence Overexpression of two independent truncation mutants in SK-N-SH neuroblastoma cells with immunofluorescence

    PMID:17956895

    Open questions at the time
    • Which step of endosomal trafficking was specifically disrupted remained unclear
    • Relevance at physiological expression levels not tested
  3. 2009 Medium

    An unbiased Drosophila genetic screen revealed the Toll signaling pathway as a major downstream effector of mutant CHMP2B toxicity, expanding the pathogenic mechanism beyond simple endosomal blockade to signaling misregulation.

    Evidence Genome-wide genetic modifier screen in Drosophila, epistasis with serpin5/Spaetzle

    PMID:19581577

    Open questions at the time
    • Whether Toll pathway activation occurs in mammalian neurons was not established
    • Whether Toll activation is a direct consequence of endosomal trapping or an indirect effect was unclear
  4. 2010 High

    Multiple studies converged to define the specific trafficking defect: mutant CHMP2B blocks endosome-lysosome fusion by constitutively binding MVBs and preventing Rab7 recruitment, while also impairing autophagic flux and dendritic spine maturation in neurons.

    Evidence Functional endocytic fusion assays in patient fibroblasts (Rab7 mechanism), LC3-II western blots, confocal morphometry and electrophysiology in hippocampal neurons with RNAi phenocopy

    PMID:20223751 PMID:20352044 PMID:20699355

    Open questions at the time
    • How CHMP2B promotes Rab7 recruitment at the molecular level was not defined
    • Whether spine maturation defects are caused by endosomal dysfunction or a distinct CHMP2B function was unknown
  5. 2011 High

    Cryo-EM visualization of CHMP2B helical filaments on membrane tubes upon VPS4 depletion revealed the structural basis of ESCRT-III polymerization and membrane remodeling by CHMP2B.

    Evidence VPS4 depletion, cryo-electron microscopy of membrane tubes in cells

    PMID:21926173

    Open questions at the time
    • Atomic-resolution structure of CHMP2B filament was not obtained
    • How VPS4 disassembles the filament at the molecular level remained unknown
  6. 2012 High

    Transgenic mouse studies definitively established a gain-of-function mechanism: mutant CHMP2B mice develop progressive p62/ubiquitin-positive neurodegeneration with axonal transport defects, while knockout and wild-type transgenic mice do not; genetic modifier studies identified syntaxin 13 as an ESCRT-III-dependent regulator of autophagosome maturation.

    Evidence Transgenic and knockout mouse histopathology; Drosophila genetic modifier screen validated by mammalian siRNA knockdown with autophagic flux assays

    PMID:22366797 PMID:22521643 PMID:24095276

    Open questions at the time
    • Whether p62-positive inclusions are causative or correlative in neurodegeneration was unclear
    • Whether syntaxin 13 acts directly on CHMP2B or in parallel was not resolved
  7. 2013 Medium

    Demonstration that mutant CHMP2B traps Notch in enlarged endosomes and drives ectopic Notch signaling—rescuable by partial Notch loss—provided evidence that receptor signaling deregulation contributes to CHMP2B-mediated neurodegeneration.

    Evidence Drosophila transgenic expression with Notch loss-of-function genetic rescue

    PMID:24158394

    Open questions at the time
    • Whether Notch pathway activation occurs in mammalian neurons expressing mutant CHMP2B was not shown
    • Other trapped signaling receptors were not systematically catalogued
  8. 2015 High

    Quantitative immuno-EM localized endogenous CHMP2B beneath the perisynaptic membrane of dendritic spines, where it forms a stable complex with other CHMPs and postsynaptic scaffolds; depletion abolished activity-induced spine enlargement and LTP, establishing a direct synaptic function for CHMP2B.

    Evidence Immuno-electron microscopy, co-IP/mass spectrometry from synaptoneurosomes, shRNA knockdown with in vivo spine density and LTP electrophysiology

    PMID:25698751

    Open questions at the time
    • The mechanism by which CHMP2B supports spine enlargement (membrane addition, receptor trafficking, or scaffold organization) was not resolved
    • Identity of the stable postsynaptic complex was not fully defined
  9. 2015 High

    Lysosomal storage pathology was confirmed in both transgenic mice expressing mutant CHMP2B at physiological levels and in FTD patient brains, validating the endolysosomal degradation block as an early feature of disease.

    Evidence Transgenic mouse model, electron microscopy, immuno-gold labelling, patient brain immunofluorescence

    PMID:26358247

    Open questions at the time
    • Whether lysosomal storage precedes or follows autophagy impairment was not temporally resolved
  10. 2018 High

    Two key mechanistic advances defined CHMP2B's biophysical behavior: in vitro reconstitution showed CHMP2B preferentially binds PI(4,5)P2-containing membranes and acts as a diffusion barrier at membrane necks, while neuronal studies demonstrated that mutant CHMP2B fails to recruit VPS4, locking it onto endolysosomes and blocking their trafficking in dendrites.

    Evidence Purified protein reconstitution on GUVs and pulled nanotubes; live imaging of endolysosomal trafficking in neurons with VPS4 interaction assay and ASO rescue

    PMID:29967034 PMID:30496365

    Open questions at the time
    • Whether the diffusion barrier function operates at endosomal necks in vivo was not tested
    • How TMEM106B ASO rescue mechanistically restores trafficking was not fully elucidated
  11. 2021 High

    CHMP2B was shown to regulate TDP-43 phosphorylation through a non-autophagic pathway by controlling CK1 kinase stability via ubiquitin-proteasome turnover, and independently, mutant CHMP2B was found to cause presynaptic synaptopathy with selective synaptic vesicle recycling defects; biophysical comparison showed CHMP2B uniquely rigidifies membranes compared to CHMP2A/CHMP3.

    Evidence Drosophila genetic screen validated in mammalian cells with CK1 ubiquitination assay; transgenic mouse histology with FM dye SV recycling; purified protein membrane mechanics measurements

    PMID:33832485 PMID:34726688 PMID:34855215

    Open questions at the time
    • Whether CK1 regulation is a direct binding interaction or mediated through endosomal signaling was not established
    • Relative contribution of pre- vs. postsynaptic dysfunction to neurodegeneration was unclear
  12. 2022 Medium

    Mutant CHMP2BIntron5 was found to sequester spastin (an endosomal microtubule-severing enzyme) into insoluble p62-positive aggregates, providing a mechanism for cytoskeletal disruption downstream of ESCRT-III dysfunction.

    Evidence Co-immunoprecipitation, subcellular fractionation in cells and mouse brain, Drosophila genetic epistasis

    PMID:36414997

    Open questions at the time
    • Whether spastin sequestration contributes to axonal transport defects was not directly tested
    • Stoichiometry of the CHMP2B-spastin interaction was not defined
  13. 2024 Medium

    CHMP2B was identified as a driver of nuclear pore complex injury in sporadic ALS: sustained CHMP2B activity promotes pathologic CHMP7 nuclear accumulation and nucleoporin POM121 loss, and partial CHMP2B knockdown rescues NPC integrity and TDP-43 mislocalization in sALS iPSC neurons.

    Evidence iPSC-derived sALS neuron model, CHMP2B knockdown, super-resolution NPC imaging, TDP-43 localization

    PMID:39709457

    Open questions at the time
    • How CHMP2B activates CHMP7 nuclear accumulation mechanistically was not resolved
    • Whether this pathway operates in FTD3 patient neurons was not tested
  14. 2025 Medium

    CHMP2B axonal transport was shown to depend on kinesin-binding protein (KBP) and to be regulated by neuronal activity; the CHMP2BIntron5 mutant loses KBP binding, resulting in aberrant bidirectional tug-of-war transport and failure to reach presynaptic boutons.

    Evidence Live axonal trafficking imaging, co-transport analysis, KBP binding assay, neuronal activity manipulation

    PMID:40021219

    Open questions at the time
    • Whether KBP interaction is direct or scaffolded was not resolved
    • Whether restoring presynaptic localization is sufficient to rescue synaptic defects was not tested
  15. 2026 High

    Discovery of a CRM1-dependent nuclear export signal in the CHMP2B C-terminus explained why the FTD3-causative CHMP2BIntron5 truncation mislocalizes to the nucleus, adding a nuclear gain-of-function mechanism to the cytoplasmic endolysosomal trafficking defect.

    Evidence CRM1 inhibition (leptomycin B), site-directed mutagenesis of NES residues, iPSC-derived cortical neuron localization

    PMID:41559796

    Open questions at the time
    • Nuclear targets or chromatin effects of mislocalized CHMP2BIntron5 were not identified
    • Whether nuclear CHMP2B contributes to NPC injury independently of CHMP7 was not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the atomic structure of CHMP2B filaments, the physiological function of CHMP2B at synapses (membrane remodeling vs. signaling scaffold), the relative pathogenic contributions of endolysosomal blockade, nuclear mislocalization, and signaling deregulation in human FTD/ALS, and whether CHMP2B's membrane repair function is relevant to neurodegeneration.
  • No atomic-resolution structure of CHMP2B filaments exists
  • Relative contribution of nuclear vs. cytoplasmic gain-of-function to disease is unknown
  • Membrane repair role has not been validated in neurons in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008289 lipid binding 2
Localization
GO:0005768 endosome 4 GO:0005764 lysosome 2 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2 GO:0005634 nucleus 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9612973 Autophagy 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-168256 Immune System 1
Partners
CHMP4BCHMP7CK1KBPSPASTSTX13TMEM106BVPS4
Complex memberships
ESCRT-III

Evidence

Reading pass · 28 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 leading to C-terminal truncation of the protein, disrupting ESCRT-III function and causing frontotemporal dementia. Genetic mapping, mRNA splicing analysis in patient tissue samples Nature genetics High 16041373
2007 C-terminally truncated CHMP2B mutants (p.Met178ValfsX2 and p.Gln165X) cause formation of large aberrant endosomal structures when overexpressed in human neuroblastoma cells, establishing that C-truncating mutations disrupt endosome function through a dominant-negative or gain-of-function mechanism. Overexpression in SK-N-SH cells, immunofluorescence microscopy Human molecular genetics High 17956895
2010 Mutant CHMP2B causes a specific disruption of endosome-lysosome fusion (but not MVB protein sorting) by constitutively binding to MVBs and preventing recruitment of Rab7, a protein required for fusion. Functional endocytic assays in patient fibroblasts, immunofluorescence, patient brain pathology analysis Human molecular genetics High 20223751
2010 Mutant CHMP2B (CHMP2BIntron5) causes aberrant lysosomal localisation and impairment of autophagy (increased LC3-II levels) when transfected into HEK-293 and COS-7 cells, forming large cytoplasmic vacuoles absent with wild-type CHMP2B. Transfection of mutant vs. wild-type CHMP2B, CD63 immunostaining, LC3-II western blot PloS one Medium 20352044
2010 CHMP2B is required for dendritic spine maturation; FTD-linked mutants (CHMP2BIntron5 and CHMP2BΔ10) reduce the proportion of mushroom-shaped large spines in hippocampal neurons and decrease frequency and amplitude of spontaneous excitatory postsynaptic currents. RNAi depletion of endogenous CHMP2B phenocopies mutant overexpression, indicating dominant-negative activity. Confocal microscopy with 3D reconstruction in cultured hippocampal neurons, electrophysiology (mEPSC recording), RNAi knockdown Journal of cell science High 20699355
2011 Full-length CHMP2B polymerizes into long rigid membrane tubes protruding from the cell surface when VPS4 is depleted; cryo-EM demonstrates CHMP2B forms a tightly packed helical lattice in close association with the inner leaflet of the membrane tube, deforming the lipid bilayer. CHMP4s relocalize to the base of CHMP2B tubes. VPS4 depletion, overexpression, cryo-electron microscopy, fluorescence microscopy The Journal of biological chemistry High 21926173
2012 Transgenic mice expressing C-terminally truncated mutant CHMP2B develop neurodegeneration through a gain-of-function mechanism: progressive p62/ubiquitin-positive (TDP-43-negative) inclusions, gliosis, and axonal swellings with amyloid precursor protein accumulation. Knockout mice and wild-type CHMP2B transgenic mice show none of these changes. Transgenic and knockout mouse generation, histopathology, immunohistochemistry Brain : a journal of neurology High 22366797
2012 Syntaxin 13 (STX13) is a genetic modifier of ESCRT-III dysfunction caused by mutant CHMP2B; knockdown of STX13 or its binding partner Vti1a in mammalian cells causes LC3-positive autophagosome accumulation and blocks autophagic flux; STX13 localizes on LC3-positive phagophores and participates in phagophore maturation into closed autophagosomes. Drosophila genetic modifier screen, mammalian siRNA knockdown, LC3 immunofluorescence, autophagic flux assay 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, increased association with Snf7-2 (ESCRT-III core), and causes autophagosome accumulation in post-mitotic neurons. Overexpression in neurons, immunofluorescence, co-immunoprecipitation, EGFR degradation assay Biochemical and biophysical research communications Medium 22521643
2013 Expression of CHMP2BIntron5 in Drosophila causes Notch accumulation in enlarged endosomes and upregulation of Notch activity; partial loss of Notch rescues eye deformities, indicating that mutant CHMP2B drives neurodegeneration-associated phenotypes through Notch misregulation in this context. Drosophila transgenic expression, genetic epistasis (Notch loss-of-function rescue), immunofluorescence FASEB journal Medium 24158394
2015 Endogenous Chmp2b concentrates beneath the perisynaptic membrane of dendritic spines (quantitative immuno-EM); Chmp2b depletion reduces dendritic branching and excitatory synapse density in vitro and in vivo and abolishes activity-induced spine enlargement and synaptic potentiation; Chmp2b is stably bound in synaptoneurosome lysates to a large complex containing other CHMP family members and postsynaptic scaffolds. Quantitative immuno-electron microscopy, co-immunoprecipitation, mass spectrometry, shRNA knockdown, in vivo spine density measurement, LTP electrophysiology The Journal of neuroscience High 25698751
2015 Mutant CHMP2B causes lysosomal storage pathology in neurons: transgenic mice expressing FTD-causative mutant CHMP2B at physiological levels develop large neuronal autofluorescent aggregates derived from the endolysosomal system, confirmed by ultrastructural analysis and immuno-gold labelling; similar aggregates are found in patient brains. Transgenic mouse model, electron microscopy, immuno-gold labelling, patient brain immunofluorescence Acta neuropathologica High 26358247
2015 TMEM106B associates with CHMP2B-positive endosomal structures; the TMEM106B T185 variant associates more strongly with CHMP2B than S185 and enhances CHMP2B(Intron5)-induced EGFR accumulation, autophagy impairment, and neurotoxicity. Co-immunoprecipitation, immunofluorescence colocalization, autophagic flux assay, neurotoxicity assay Molecular brain Medium 26651479
2018 Mutant CHMP2B stably incorporates onto neuronal endolysosomes, rendering them unable to traffic within dendrites. This is mechanistically due to inability of mutant CHMP2B to recruit the ATPase VPS4, which is required for CHMP2B release from endosomal membranes. TMEM106B antisense oligonucleotide treatment rescues both impaired trafficking and increased dendritic branching. Live imaging of endolysosomal trafficking, CHMP2B-VPS4 interaction assay, antisense oligonucleotide rescue in neurons expressing physiological levels of mutant CHMP2B Brain : a journal of neurology High 30496365
2018 CHMP2B polymerization on reconstituted membrane nanotubes acts as a diffusion barrier: CHMP2B (full-length and ΔC) preferentially binds membranes containing PI(4,5)P2, accumulates at nanotube necks, and prevents diffusion of PI(4,5)P2 lipids and membrane-bound proteins across the neck. In vitro reconstitution in giant unilamellar vesicles, pulled membrane nanotubes, fluorescence microscopy, purified protein binding assays Journal of cell science High 29967034
2009 In a Drosophila model of FTD3, serpin5 (a serine protease inhibitor) suppresses mutant CHMP2B toxicity by acting as a negative regulator of the Toll pathway, blocking proteolytic activation of Spaetzle (Toll receptor ligand) extracellularly; the Toll signaling pathway is identified as a major pathway misregulated by mutant CHMP2B in vivo. Genome-wide genetic modifier screen in Drosophila, epistasis analysis, gain/loss-of-function genetics Proceedings of the National Academy of Sciences of the United States of America Medium 19581577
2021 CHMP2B binding to membranes is enhanced by PI(4,5)P2 lipids (unlike CHMP2A which requires CHMP3 and lacks lipid specificity); CHMP2B strongly rigidifies membranes upon polymerization while CHMP2A+CHMP3 does not, demonstrating distinct mechanical properties between ESCRT-III isoforms. In vitro binding assays with purified proteins and biomimetic membrane systems, membrane mechanics measurements, fluorescence microscopy BMC biology High 33832485
2021 CHMP2B regulates TDP-43 phosphorylation and cytotoxicity independently of autophagy through modulation of CK1 kinase: CHMP2B negatively regulates ubiquitination and proteasome-mediated turnover of CK1, thereby controlling CK1 protein levels and TDP-43 phosphorylation. Drosophila genetic screen, mammalian cell knockdown/overexpression, CK1 ubiquitination assay, TDP-43 phosphorylation western blot The Journal of cell biology High 34726688
2021 Mutant CHMP2B causes a novel synaptopathy: selective retention of presynaptic synaptic vesicle trafficking proteins in aged transgenic mice, increased presynaptic endosomes, defective synaptic vesicle recycling and altered functional SV pools, while postsynaptic proteins are lost. Transgenic mouse histology, ultrastructural analysis of primary cortical cultures, FM dye SV recycling assay Journal of neurochemistry Medium 34855215
2022 Mutant CHMP2BIntron5 associates with spastin with greater affinity than wild-type CHMP2B and colocalizes in p62-positive aggregates; spastin is sequestered from the soluble cytoplasmic fraction to the insoluble fraction in cells and mouse brain neurons expressing CHMP2BIntron5; genetic knockdown of spastin enhances CHMP2BIntron5 toxicity in Drosophila. Co-immunoprecipitation, immunofluorescence colocalization, subcellular fractionation, Drosophila genetic epistasis Acta neuropathologica communications Medium 36414997
2022 SIRT6 regulates CHMP2B levels in the heart by decreasing acetylation of FoxO1, promoting its transcriptional activation of Atrogin-1 (a muscle-specific ubiquitin ligase), which subsequently mediates ubiquitin-proteasome degradation of CHMP2B. Mouse cardiac SIRT6 heterozygous knockout, FoxO1 acetylation assay, Atrogin-1 transcriptional reporter, CHMP2B degradation assay Journal of cardiovascular translational research Medium 35235147
2020 Partial loss of Ik2 (fly TBK1 homologue) enhances mutant CHMP2B toxicity in the fly eye while Ik2 overexpression suppresses it; loss of Spn-F (Ik2 phosphorylation target), dynein light chain (cut up), or Hook (early endosome transport adaptor) also enhances mutant CHMP2B toxicity, implicating early endosome transport as a contributing pathway. Drosophila genetic epistasis, interactome analysis Scientific reports Medium 32848189
2024 CHMP2B promotes CHMP7-mediated nuclear pore complex (NPC) injury in sporadic ALS neurons: sustained CHMP2B-dependent activation is sufficient to cause pathologic CHMP7 nuclear accumulation and POM121 (nucleoporin) reduction; partial knockdown of CHMP2B alleviates NPC injury and downstream TDP-43 dysfunction in sALS iPSC-derived neurons. iPSC-derived neuron model of sALS, CHMP2B knockdown, super-resolution microscopy, NPC integrity assay, TDP-43 localization Acta neuropathologica communications Medium 39709457
2026 Wild-type CHMP2B contains a nuclear export signal (NES) in its C-terminus that mediates CRM1-dependent nuclear export; the FTD3-causative CHMP2BIntron5 mutation removes this NES, causing mislocalization of CHMP2BIntron5 to the nucleus of iPSC-derived cortical neurons. Site-directed mutagenesis of key hydrophobic residues in the NES abolishes nuclear export. CRM1 inhibition (leptomycin B), site-directed mutagenesis, iPSC-derived cortical neuron localization, functional NES assay Acta neuropathologica communications High 41559796
2025 CHMP2B axonal transport and recruitment to presynaptic boutons is regulated by neuronal activity and requires kinesin-binding protein (KBP); CHMP2BIntron5 shows deficient binding to KBP, resulting in little processive movement or presynaptic localization and instead oscillatory tug-of-war behavior between kinesin and dynein. Live axonal trafficking imaging in neurons, co-transport analysis, KBP binding assay, neuronal activity manipulation Life science alliance Medium 40021219
2023 CHMP2B T104N mutation causes preferential accumulation in the Golgi body (rather than ESCRT-like cytoplasmic structures), triggers Golgi stress signaling via Arf4 upregulation, and inhibits neuronal process elongation; Arf4 knockdown recovers the neuronal process elongation phenotype. Transfection in N1E-115 neuronal cell line, immunofluorescence subcellular localization, siRNA knockdown, neurite measurement Neurology international Medium 37606396
2025 Truncation mutation of CHMP2B disrupts late endosome-lysosome fusion; CHMP2BIntron5 overexpression upregulates HSP70, which promotes TDP-43 aggregate degradation by enhancing recruitment to juxtanuclear quality control compartments. Transcriptomic analysis, overexpression in cells, immunofluorescence, TDP-43 aggregation assay Neurochemistry international Low 40316175
2024 CHMP2B and ANXA11 act sequentially in membrane repair: ESCRT-III (including CHMP2B) assembles at sites of membrane damage only after initial membrane sealing by Annexins, and acts to shed damaged membranes from the cell; FTD/ALS-associated mutations in CHMP2B compromise this repair process. Live cell imaging of membrane damage response, temporal recruitment analysis, loss-of-function with disease mutants bioRxivpreprint Medium

Source papers

Stage 0 corpus · 73 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 670 16041373
2006 ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B). Neurology 321 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 147 20223751
2007 CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro. Human molecular genetics 125 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 80 26358247
2011 Frontotemporal dementia caused by CHMP2B mutations. Current Alzheimer research 73 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 69 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 60 24095276
2010 CHMP2B mutants linked to frontotemporal dementia impair maturation of dendritic spines. Journal of cell science 60 20699355
2009 The role of CHMP2B in frontotemporal dementia. Biochemical Society transactions 51 19143633
2010 Immunopositivity for ESCRT-III subunit CHMP2B in granulovacuolar degeneration of neurons in the Alzheimer's disease hippocampus. Neuroscience letters 50 20420883
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 21 32801000
2010 CHMP2B mutations are rare in French families with frontotemporal lobar degeneration. Journal of neurology 20 20625756
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
2021 The ESCRT-III protein VPS4, but not CHMP4B or CHMP2B, is pathologically increased in familial and sporadic ALS neuronal nuclei. Acta neuropathologica communications 16 34281622
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
2012 Reversal of pathology in CHMP2B-mediated frontotemporal dementia patient cells using RNA interference. The journal of gene medicine 12 22786763
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 11 32848189
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
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
2017 TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3). Neurobiology of aging 6 28888721
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
2021 Differential levels of CHMP2B, LLPH, and SLC25A51 proteins in secondary renal amyloidosis. Expert review of proteomics 2 33583303
2025 Truncation mutation of CHMP2B disrupts late endosome function but reduces TDP-43 aggregation through HSP70 upregulation. Neurochemistry international 1 40316175
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
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