Affinage

VPS35

Vacuolar protein sorting-associated protein 35 · UniProt Q96QK1

Length
796 aa
Mass
91.7 kDa
Annotated
2026-06-11
100 papers in source corpus 48 papers cited in narrative 48 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VPS35 is the central cargo-recognition subunit of the retromer complex, an evolutionarily conserved machinery that retrieves transmembrane cargo from endosomes to the trans-Golgi network or plasma membrane (PMID:1498362, PMID:9105038). It assembles into a stable trimer with VPS29 and VPS26: VPS35 and VPS29 form a biologically stable sub-complex whose subunits stabilize each other, while VPS26 binds VPS35 through a mobile C-terminal loop of its arrestin fold (PMID:16732284, PMID:25937119). Retromer is recruited to late endosomes by activated Rab7, an interaction allosterically enhanced by VPS26 association with VPS35 (PMID:25367362), and a conserved N-terminal PRLYL/R107 motif is essential for sub-complex assembly (PMID:17916227). VPS35 drives endosomal tubule and transport-carrier formation by directly binding the FAM21 subunit of the actin-nucleating WASH complex and SNX3 (PMID:22070227, PMID:33347683). Through this machinery VPS35 sorts a broad cargo repertoire including the CI-M6PR/cathepsin D axis, BACE1, sortilin, Lamp2a, Trem2, DRD1, DMT1, and EGFR, linking retromer to amyloid processing, chaperone-mediated autophagy, microglial inflammation, dopaminergic signaling, iron handling, and receptor-driven proliferation (PMID:21040701, PMID:22105352, PMID:24152121, PMID:26203154, PMID:27717139, PMID:27460146, PMID:30809369, PMID:36738481). Beyond canonical sorting, VPS35 participates in a retromer-dependent mitochondria-to-peroxisome route delivering the MAPL ligase via mitochondria-derived vesicles (PMID:20619655) and in non-canonical endosomal turnover of damaged mitochondrial nucleoids (PMID:36344526). The Parkinson's-disease mutation D620N is correctly folded and retains VPS29/VPS26 binding but selectively weakens VPS35 affinity for FAM21, impairing WASH recruitment, endosome-to-TGN transport, and cargo sorting (PMID:24152121, PMID:24980502, PMID:24819384, PMID:33347683); D620N additionally hyperactivates LRRK2 kinase to elevate Rab8A/Rab10/Rab12 phosphorylation and assemble a RILPL1–TMEM55B lysosomal module (PMID:29743203, PMID:38091401), increases VPS35 interaction with the fission GTPase DLP1 to drive mitochondrial fragmentation and bioenergetic failure (PMID:26618722, PMID:28040727, PMID:28765075, PMID:33745227), and impairs PINK1/Parkin mitophagy (PMID:34127073). VPS35 is itself ubiquitinated on C-terminal lysines by parkin in a non-degradative manner that supports WASH-dependent sorting of cargoes such as ATG9A (PMID:29893854). VPS35 mutations cause autosomal-dominant Parkinson's disease, and D620N knock-in mice recapitulate cardinal PD features (PMID:33745227).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1992 High

    Established that VPS35 is required for vacuolar protein sorting, defining its foundational role in routing hydrolases to the lysosome/vacuole.

    Evidence Gene disruption with subcellular fractionation and CPY sorting assays in S. cerevisiae

    PMID:1498362

    Open questions at the time
    • Did not identify the molecular partners or cargo-recognition mechanism
    • Cargo specificity (only CPY missorted) left alternative pathways undefined
  2. 1997 High

    Defined VPS35 as a receptor-retrieval factor that returns the sorting receptor Vps10p from the endosome to the Golgi, framing retromer as a retrograde recycling machine.

    Evidence Temperature-conditional allele, fractionation, epistasis, and co-fractionation in yeast

    PMID:9105038

    Open questions at the time
    • Direct VPS35–receptor binding inferred from co-fractionation, not demonstrated structurally
    • Mechanism of subunit assembly not resolved
  3. 2006 High

    Resolved how VPS26 integrates into retromer, mapping VPS35 binding to an arrestin-fold loop and linking complex assembly to endosomal localization and cargo sorting.

    Evidence X-ray crystallography, mutagenesis, and yeast CPY complementation

    PMID:16732284

    Open questions at the time
    • Structure of full VPS35 and the cargo-binding surface not solved
    • Did not address mammalian disease cargo
  4. 2007 Medium

    Identified the N-terminal PRLYL/R107 motif as critical for retromer sub-complex assembly, showing assembly defects displace VPS35 to the cytosol and disrupt receptor distribution.

    Evidence Yeast dominant-negative assay, co-IP, fractionation, and β-cell immunofluorescence

    PMID:17916227

    Open questions at the time
    • Single-lab characterization of the R107W variant
    • Functional consequence for specific mammalian cargo limited
  5. 2010 Medium

    Extended retromer beyond endosome-to-Golgi sorting by showing VPS35/VPS26 mediate a mitochondria-to-peroxisome route for MAPL via mitochondria-derived vesicles.

    Evidence Unbiased Co-IP screen, confocal imaging, siRNA knockdown, and MAPL delivery assay

    PMID:20619655

    Open questions at the time
    • Whether VPS35 directly recognizes MAPL cargo not established
    • Single-lab finding without reciprocal in vivo validation
  6. 2011 High

    Connected VPS35 to Alzheimer pathology by demonstrating it retrieves BACE1 from endosomes, with loss elevating Aβ in vivo.

    Evidence Reciprocal Co-IP, Vps35 hemizygous Tg2576 mice, BACE1 activity, and Aβ ELISA

    PMID:22105352

    Open questions at the time
    • Direct vs indirect BACE1 binding not fully resolved
    • Did not address PD-mutant effect on this cargo
  7. 2012 Medium

    Identified the direct VPS35–FAM21 interaction as the mechanism recruiting the WASH actin machinery to endosomes, coupling retromer to actin-dependent carrier formation.

    Evidence Co-IP, endosomal localization, and FAM21-tail overexpression cell-spreading assay

    PMID:22070227

    Open questions at the time
    • Binding interface on VPS35 not mapped at residue level here
    • Did not test disease mutations
  8. 2013 Medium

    Showed the PD-linked D620N mutant is folded and retains VPS29/VPS26 binding yet redistributes endosomes and disrupts cathepsin D trafficking, reframing D620N as a sorting defect rather than a folding defect.

    Evidence Folding analysis, Co-IP, localization, and cathepsin D trafficking in cells and patient fibroblasts

    PMID:24152121

    Open questions at the time
    • The specific interaction lost was not yet identified
    • Mechanism linking cathepsin D defect to α-synuclein not directly shown
  9. 2014 High

    Pinpointed the primary D620N defect as a ~2-fold reduced FAM21 affinity that selectively impairs endosome-to-TGN transport and WASH-dependent autophagy/ATG9A trafficking.

    Evidence SILAC interactome and ITC affinity measurement plus autophagy/ATG9A and WASH localization assays in patient fibroblasts

    PMID:24819384 PMID:24980502

    Open questions at the time
    • Did not explain mitochondrial or LRRK2 phenotypes of D620N
    • Quantitative link from reduced FAM21 affinity to neurodegeneration unresolved
  10. 2014 Medium

    Established the membrane-recruitment logic of retromer by showing Rab7 binds VPS35 N-terminal regions and VPS26 allosterically boosts this affinity.

    Evidence FRET in HeLa cells, biophysical binding assays, and mutagenesis

    PMID:25367362

    Open questions at the time
    • Structural basis of the Rab7–VPS35 interface not resolved
    • Single-lab measurement
  11. 2015 High

    Linked VPS35 cargo sorting directly to α-synuclein clearance by showing it retrieves the CMA receptor Lamp2a, with rescue restoring α-synuclein degradation.

    Evidence Conditional Vps35 KO in DA neurons, Lamp2a trafficking and CMA assays, and Lamp2a rescue

    PMID:26203154

    Open questions at the time
    • Whether VPS35 binds Lamp2a directly not established
    • Relative contribution of CMA vs other clearance routes unquantified
  12. 2015 High

    Defined mitochondrial pathways downstream of VPS35 dysfunction: enhanced DLP1 interaction driving fission and MUL1-mediated MFN2 degradation causing DA neuron loss.

    Evidence Co-IP, fission-inhibitor rescue, MUL1 siRNA rescue, and brain tissue analysis from PD cases

    PMID:26321632 PMID:26618722

    Open questions at the time
    • How a retromer cargo-sorting protein engages mitochondrial fission machinery mechanistically unclear
    • MUL1 and DLP1 axes not fully reconciled
  13. 2015 Medium

    Implicated VPS35 in synaptic function via trafficking of AMPA receptor subunits, with D620N behaving as loss-of-function for synaptic transmission.

    Evidence Co-IP, electrophysiology, surface AMPAR assays in mouse and D620N iPSC neurons, and rescue overexpression

    PMID:25416282 PMID:26521016

    Open questions at the time
    • Direct vs adaptor-mediated AMPAR binding not resolved
    • Single-lab synaptic measurements
  14. 2016 Medium

    Broadened the cargo repertoire to Trem2 and DRD1 recycling, connecting VPS35 to microglial inflammation and dopaminergic signaling, with D620N selectively failing recycling.

    Evidence Co-IP, recycling assays, inflammatory cytokine and CREB/ERK readouts with knockdown/overexpression

    PMID:27460146 PMID:27717139

    Open questions at the time
    • Direct cargo-binding interfaces not mapped
    • Single-lab studies for each cargo
  15. 2017 High

    Mapped the DLP1–VPS35 interaction to a conserved DLP1 FLV motif and demonstrated decoy-peptide rescue of D620N mitochondrial defects, providing mechanistic and translational validation.

    Evidence Motif mutagenesis, Co-IP, decoy peptide, and respiration assays in cells and patient fibroblasts

    PMID:28040727

    Open questions at the time
    • Why D620N increases this interaction at the structural level unexplained
    • In vivo efficacy of peptide not tested here
  16. 2018 High

    Revealed that VPS35 controls LRRK2 kinase activity, with D620N strikingly elevating LRRK2-mediated Rab8A/Rab10/Rab12 phosphorylation in vivo and in patient cells.

    Evidence D620N knock-in mice, phospho-Rab assays, patient neutrophils/monocytes, and VPS35 knockdown across cell lines

    PMID:29743203

    Open questions at the time
    • Molecular mechanism by which VPS35 regulates LRRK2 not defined
    • Link between Rab hyperphosphorylation and cargo sorting unresolved
  17. 2018 High

    Showed parkin directly ubiquitinates VPS35 on C-terminal lysines in a non-degradative manner required for WASH-dependent ATG9A sorting, integrating two PD genes.

    Evidence Ubiquitination assay, MS site identification, parkin KO mouse brain, and ATG9A trafficking

    PMID:29893854

    Open questions at the time
    • How atypical ubiquitin chains alter retromer function mechanistically unclear
    • Functional consequence beyond ATG9A not surveyed
  18. 2020 Medium

    Demonstrated that missorting of specific cargoes (sortilin1, Cdk5/p35) to lysosomes upon VPS35 loss drives neurodegenerative phenotypes, with cargo suppression rescuing defects.

    Evidence Conditional Vps35 KO, cargo lysosomal localization, siRNA rescue/phenocopy, and Cdk5 inhibitor rescue

    PMID:31907392 PMID:31995153

    Open questions at the time
    • Direct cargo-binding for each not established
    • Single-lab models
  19. 2021 High

    Connected D620N to impaired PINK1/Parkin mitophagy by showing it inhibits PINK1 stabilization and Parkin recruitment, and reproduced cardinal PD pathology in aged knock-in mice.

    Evidence CRISPR D620N knock-in cells with mitophagy assays and aged D620N knock-in mouse phenotyping with DLP1 Co-IP

    PMID:33745227 PMID:34127073

    Open questions at the time
    • Causal ordering of fission, bioenergetic and mitophagy defects unresolved
    • Mechanism by which D620N blocks PINK1 accumulation unclear
  20. 2023 High

    Resolved the lysosomal arm of D620N signaling, showing LRRK2-driven phospho-Rabs recruit RILPL1 to TMEM55B at the lysosome and reshape the lysosomal proteome.

    Evidence Quantitative lysosomal proteomics, Co-IP, interface mutagenesis, LRRK2 inhibition, and RILPL1/TMEM55B knockout mice

    PMID:38091401

    Open questions at the time
    • Physiological consequence of the RILPL1–TMEM55B module for neurodegeneration unclear
    • Connection to retromer cargo sorting not directly drawn
  21. 2023 Medium

    Demonstrated in vivo that LRRK2 kinase inhibition normalizes dopamine transporter function specifically in D620N (not haploinsufficient) mice, establishing a functional VPS35–LRRK2 axis governing dopamine transmission.

    Evidence D620N and haploinsufficient mice, MLi-2 treatment, phospho-Rab blots, voltammetry, and behavior

    PMID:38110354

    Open questions at the time
    • Whether DAT is a direct retromer cargo not shown
    • Distinct phenotypes of gain-of-function D620N vs haploinsufficiency mechanistically separate

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single D620N substitution simultaneously weakens FAM21 binding, hyperactivates LRRK2 kinase, and rewires mitochondrial fission remains mechanistically unresolved at the structural level.
  • No structure explaining D620N gain-of-function toward LRRK2 and DLP1
  • The molecular link between cytosolic retromer sorting and mitochondrial/lysosomal phenotypes is not unified
  • Direct cargo-binding surfaces on VPS35 for most named cargoes remain unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 3 GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005768 endosome 4 GO:0005739 mitochondrion 3 GO:0005764 lysosome 3 GO:0005794 Golgi apparatus 3 GO:0005829 cytosol 3
Pathway
R-HSA-1643685 Disease 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9609507 Protein localization 4 R-HSA-9612973 Autophagy 4 R-HSA-162582 Signal Transduction 3
Partners
BACE1DLP1FAM21RAB7SNX3VPS10/SORTILINVPS26VPS29
Complex memberships
WASH complex (via FAM21)retromer (VPS35–VPS29–VPS26)

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Vps35p is a peripheral membrane protein (~80% associates with a membranous particulate fraction) required for vacuolar protein sorting; vps35 null mutants quantitatively missort and secrete carboxypeptidase Y (CPY) but retain most PrA, PrB, and ALP, indicating alternative sorting pathways exist for different vacuolar hydrolases. Gene disruption (null allele), subcellular fractionation, vacuolar protein sorting assay in S. cerevisiae Molecular biology of the cell High 1498362
1997 Vps35p, together with Vps29p and Vps30p, is required for retrieval of the vacuolar sorting receptor Vps10p from the prevacuolar endosome back to the Golgi; loss of VPS35 shifts Vps10p from the Golgi to the vacuolar membrane via a Pep12p-dependent (pre-vacuolar endosomal t-SNARE) but Sec1p-independent route; Vps35p co-fractionates with Vps10p even in vps29 mutants, suggesting direct interaction. Temperature-conditional VPS35 allele, subcellular fractionation, epistasis analysis with pep12 and sec1 mutants, co-fractionation in S. cerevisiae The Journal of cell biology High 9105038
2006 Crystal structure of human Vps26A (2.1-Å resolution) reveals an arrestin-fold with two curved β-sandwich domains; the Vps35-binding site maps to a mobile loop (residues 235–246) near the tip of the C-terminal domain; hydrophobic residues and a glycine in this loop are required for Vps26 integration into the retromer complex and endosomal localization, and for yeast Vps26 function in CPY sorting. X-ray crystallography, mutagenesis, endosomal localization assay, yeast CPY sorting complementation Nature structural & molecular biology High 16732284
2007 VPS35 interacts (indirectly) with the LRP6 intracellular domain; an N-terminal deletion mutant of VPS35 reduces canonical Wnt signaling in HEK-293 cells expressing Wnt-1, placing retromer-mediated endosomal trafficking upstream of Wnt signal transduction. GST fusion protein pulldown, luciferase Tcf reporter assay in HEK-293 cells Neurobiology of disease Low 17239604
2007 A conserved PRLYL motif in the N-terminal domain of Vps35 is critical for retromer subcomplex assembly; mutation of the corresponding R107W in human VPS35 displaces the protein to the cytosol, prevents co-precipitation with Vps26, and abrogates dominant-negative trafficking in yeast; in pancreatic β-cells the R107W mutant shifts from peripheral endosomes to a juxtanuclear compartment, altering mannose phosphate receptor and insulin distribution. Yeast dominant-negative assay, co-immunoprecipitation, subcellular fractionation, immunofluorescence in pancreatic β-cells Traffic (Copenhagen, Denmark) Medium 17916227
2007 Drosophila Vps35 loss inhibits scavenger receptor ligand endocytosis, mislocalizes endocytic proteins and receptors, leads to overproliferation of blood cells (tumor suppressor function), causes upregulation of TGFβ/BMP signaling at the neuromuscular junction, and negatively regulates actin polymerization; genetic interactions indicate actin dysregulation underlies some endocytic and signaling defects. RNAi knockdown in Drosophila S2 cells and larvae, endocytosis assay, immunofluorescence, genetic interaction analysis Journal of cell science Medium 18057029
2010 Retromer component Vps35, together with Vps26, is found in complex with the mitochondrial SUMO E3 ligase MAPL; Vps35 is recruited to mitochondria-derived vesicles (MDVs); silencing Vps35 or Vps26A significantly reduces delivery of MAPL from mitochondria to peroxisomes, defining a retromer-dependent mitochondria-to-peroxisome trafficking route. Unbiased co-immunoprecipitation screen, confocal imaging, siRNA knockdown, MAPL delivery assay Current biology : CB Medium 20619655
2010 The Vps26b-Vps29-Vps35 retromer sub-complex mediates transport of sortilin from endosomes to the trans-Golgi network; Vps26b-deficient mice lack this specific complex (while the Vps26a-Vps29-Vps35 complex persists) and show ~20% increased sortilin levels, with normal SorLA. Vps26b knockout mice, co-immunoprecipitation, Western blot quantification of sortilin/SorLA Biochemical and biophysical research communications Medium 21040701
2011 VPS35 interacts with BACE1 (β-secretase) and promotes its endosome-to-Golgi retrieval; loss of VPS35 function in the mouse hippocampus increased BACE1 activity, enriched BACE1 in endosomes (rather than trans-Golgi), elevated Aβ levels, and accelerated Alzheimer's disease-like phenotypes in Tg2576 mice. Co-immunoprecipitation, immunofluorescence, Vps35 hemizygous deletion in Tg2576 mice, BACE1 activity assay, Aβ ELISA The Journal of cell biology High 22105352
2012 The WASH complex is recruited to endosomes via interaction of its FAM21 subunit's long unstructured tail with VPS35; this interaction is necessary and sufficient to target the WASH complex to endosomes; overexpression of the FAM21 tail increases cytoplasmic WASH complex and causes cell-spreading defects, implicating WASH-retromer in mobilizing membrane into the endosome-to-cell-surface pathway. Co-immunoprecipitation, endosomal localization assays, FAM21-tail overexpression cell-spreading assay The Biochemical journal Medium 22070227
2012 VPS35 is required for retrograde trafficking of BACE1 in developing hippocampal neurons; Vps35 depletion impairs apical dendritic growth, reduces dendritic spines, and causes swollen commissural axons; suppression of BACE1 expression partially rescues both dendritic and axonal deficits, identifying BACE1 as a critical VPS35 cargo in vivo. In utero electroporation of microRNA against Vps35, immunofluorescence, dendritic/axonal morphometry, BACE1 rescue experiment in neonatal mice Biology open Medium 23259059
2013 VPS35 regulates RANK trafficking; VPS35 loss alters RANKL-induced RANK distribution, enhances RANKL sensitivity, sustains RANKL signaling, and increases hyperresorptive osteoclast formation; hemizygous Vps35 deletion in mice causes hyperresorptive osteoclastogenesis, decreased bone formation, and osteoporotic deficits. VPS35 loss-of-function in osteoclast cultures and Vps35+/− mice, RANK distribution by immunofluorescence, RANKL signaling assays, micro-CT bone analysis The Journal of cell biology Medium 23509071
2013 The PD-linked VPS35 D620N mutant is correctly folded and retains binding to Vps29 and Vps26A with wild-type affinity, but its expression redistributes retromer-positive endosomes to a perinuclear localization (enlarged endosomes), disrupts trafficking of cathepsin D (a CI-M6PR ligand responsible for α-synuclein degradation), while still interacting with CI-M6PR cargo. Protein folding analysis, co-immunoprecipitation, immunofluorescence subcellular localization, cathepsin D trafficking assay in cell lines and patient fibroblasts Traffic (Copenhagen, Denmark) Medium 24152121
2014 VPS35 D620N mutation perturbs endosome-to-TGN transport but not endosome-to-plasma membrane recycling; SILAC-based interactome comparison reveals the primary defect is a 2.2-fold decrease in affinity for FAM21 (WASH complex component), measured by isothermal calorimetry; confirmed in patient fibroblasts. SILAC-based quantitative proteomics (interactome), isothermal calorimetry, retrograde transport assay, patient fibroblast analysis Current biology : CB High 24980502
2014 VPS35 D620N mutant associates poorly with the WASH complex and impairs WASH recruitment to endosomes; autophagy is impaired in cells expressing PD-mutant VPS35 or lacking WASH; the autophagy defect is partly explained by abnormal trafficking of the autophagy protein ATG9A. Co-immunoprecipitation, endosomal localization of WASH, autophagy flux assays, ATG9A trafficking assay Nature communications High 24819384
2014 Retromer depletion (VPS35 knockdown) increases lysosomal turnover of the mannose 6-phosphate receptor, impairs maturation of cathepsin D, and leads to accumulation of α-synuclein in lysosomes; in Drosophila, VPS35 knockdown increases detergent-insoluble α-synuclein and exacerbates locomotor impairment and neurodegeneration in α-synuclein-expressing flies. siRNA knockdown, cathepsin D maturation assay, α-synuclein solubility assay, Drosophila locomotor and eye phenotype analysis Neurobiology of disease Medium 25107340
2014 Rab7 recruits retromer to late endosomes via direct interactions with N-terminal conserved regions in Vps35; association of Vps26 with Vps35 allosterically increases affinity between the Vps sub-complex and activated Rab7; a mutation disrupting the Vps35–Vps26 interaction perturbs Rab7-mediated retromer recruitment to endosomes in HeLa cells. FRET assay in HeLa cells, biophysical binding measurements, mutagenesis Traffic (Copenhagen, Denmark) Medium 25367362
2014 VPS35 localizes to dendritic spines and is involved in trafficking of AMPA-type glutamate receptor subunits (GluA1/GluA2); VPS35 D620N acts as a loss-of-function mutation with respect to synaptic transmission and AMPAR recycling in mouse cortical neurons and iPSC-derived dopamine neurons from D620N carriers, altering excitatory synaptic transmission and AMPAR surface expression. Immunofluorescence localization, electrophysiology (mEPSC recording), AMPAR surface expression assay, iPSC-derived neuron model Human molecular genetics Medium 25416282
2014 Genetic interaction between VPS35 and EIF4G1 in yeast and worm models: EIF4G1 upregulation causes protein misfolding defects rescued by sortilin expression downstream of VPS35, placing sortilins in a VPS35-dependent pathway; interactions extend to α-synuclein pathobiology. Yeast genetic modifier screen, epistasis analysis, C. elegans and transgenic mouse models Neuron Medium 25533483
2015 VPS35 deficiency or D620N mutation in dopamine neurons impairs endosome-to-Golgi retrieval of Lamp2a (CMA receptor), accelerating Lamp2a degradation; this reduces chaperone-mediated autophagy and leads to α-synuclein accumulation; re-expression of Lamp2a in VPS35-deficient neurons reduces α-synuclein, establishing a VPS35–Lamp2a–α-synuclein pathway. Conditional Vps35 knockout in DA neurons, endosome-to-Golgi trafficking assay for Lamp2a, immunofluorescence, CMA assay, α-synuclein quantification, Lamp2a rescue experiment The Journal of neuroscience High 26203154
2015 VPS35 deficiency or D620N mutation increases mitochondrial E3 ubiquitin ligase MUL1, leading to ubiquitin-mediated degradation of mitofusin 2 (MFN2), mitochondrial fragmentation, and DA neuron loss; suppression of MUL1 rescues MFN2 levels and DA neuron loss but not α-synuclein accumulation. Conditional Vps35 KO in DA neurons, MUL1/MFN2 Western blot, MUL1 siRNA rescue, immunofluorescence of mitochondrial morphology Cell reports High 26321632
2015 PD-associated VPS35 mutants (D620N) cause mitochondrial fragmentation and cell death through increased interaction with dynamin-like protein 1 (DLP1/Drp1), enhancing turnover of mitochondrial DLP1 complexes via MDV-dependent trafficking to lysosomes; oxidative stress increases VPS35–DLP1 interaction; inhibition of mitochondrial fission prevents VPS35 mutant-induced mitochondrial deficits; VPS35–DLP1 interaction is increased in brains of sporadic PD cases. Co-immunoprecipitation, mitochondrial morphology analysis, cell death assay, DLP1 complex turnover assay, fission inhibitor rescue, brain tissue Co-IP from sporadic PD cases Nature medicine High 26618722
2015 VPS35 deficiency impairs dendritic spine maturation and decreases glutamatergic transmission; VPS35 interacts with AMPA receptor subunits GluA1 and GluA2; GluA1 and GluA2 are significantly reduced in synaptosomal and PSD fractions from VPS35-deficient brain; GluA2 overexpression (but not GluA1) partially restores spine maturation in VPS35-deficient neurons. Co-immunoprecipitation, synaptosomal fractionation, surface AMPAR quantification, dendritic spine analysis, rescue overexpression Molecular brain Medium 26521016
2015 VPS29 and VPS35 form a biologically stable sub-complex in vivo; deficiency of VPS35 or VPS29 causes degradation of the other retromer subunits, whereas VPS26 deficiency does not affect VPS29 and VPS35 levels; VPS26–VPS35 sub-complex is more susceptible to ubiquitin-proteasome degradation than VPS29–VPS35. siRNA knockdown of individual subunits, Western blot, in vitro sub-complex formation assay, proteasome inhibitor treatment FEBS letters Medium 25937119
2016 VPS35 binds farnesylated (but not palmitoylated or GTP-loaded) N-Ras in the cytosol as part of a high-molecular-weight complex; VPS35 silencing increases N-Ras association with cytoplasmic vesicles, diminishes GTP loading of Ras, and inhibits MAPK signaling and growth of N-Ras-dependent melanoma cells. Affinity purification and mass spectrometry, co-immunoprecipitation, N-Ras GTP-loading assay, MAPK signaling assay, cell growth assay with VPS35 siRNA The Journal of cell biology Medium 27502489
2016 Vps35 regulates recycling of Trem2 from endosomes to the plasma membrane in microglia; Trem2 is internalized via clathrin-dependent endocytosis and recycled through Vps35 (not Rab11); Vps35 knockdown causes Trem2 accumulation in lysosomes without degradation and leads to excessive LPS-induced iNOS/IL-6 pro-inflammatory responses; AD-associated R47H Trem2 mutant fails to interact with Vps35 and is unstable. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, clathrin inhibition assay, inflammatory cytokine measurement, Trem2 overexpression rescue Traffic (Copenhagen, Denmark) Medium 27717139
2016 VPS35 interacts with dopamine receptor D1 (DRD1) and promotes its recycling to the cell surface after endocytosis; VPS35 overexpression/knockdown increases/decreases DRD1 surface levels and downstream CREB/ERK phosphorylation; the D620N mutant retains DRD1 binding but fails to promote DRD1 recycling or rescue CREB/ERK signaling. Co-immunoprecipitation, surface receptor recycling assay, CREB/ERK phosphorylation Western blot, VPS35 overexpression and siRNA knockdown Neurobiology of aging Medium 27460146
2016 Parkinson's disease-associated Vps35 R524W variant (but not P316S) is a loss-of-function mutation: it shows reduced association with the retromer regulatory network and dysregulated endosomal receptor sorting; R524W expression causes intracellular α-synuclein-positive aggregate accumulation; R55 small molecule partially rescues R524W endosomal association. Co-immunoprecipitation, endosomal localization assay, α-synuclein immunofluorescence, pharmacological rescue with R55 The Journal of biological chemistry Medium 27385586
2017 A conserved FLV motif in the C-terminus of DLP1 mediates interaction with VPS35; a decoy peptide based on this motif blocks VPS35–DLP1 interaction, inhibits recycling of mitochondrial DLP1 complexes, and rescues D620N-induced mitochondrial fragmentation and respiratory deficits in both M17 cells and patient fibroblasts. Mutagenesis of FLV motif, Co-IP, decoy peptide treatment, mitochondrial morphology and respiration assays in cell lines and patient fibroblasts Human molecular genetics High 28040727
2017 Drosophila Vps35 loss affects synaptic vesicle recycling and dopaminergic synaptic release; dLRRK together with Rab5 and Rab11 participates in the same synaptic vesicle recycling pathway; manipulation of dLRRK/Rab5/Rab11 activity improves vps35 synaptic phenotypes, placing VPS35 and LRRK2 in a common endosomal synaptic vesicle recycling pathway. Drosophila genetics, synaptic vesicle recycling assay, dopamine release measurement, genetic interaction analysis Human molecular genetics Medium 28482024
2017 VPS35 promotes lysosomal clearance of the parkin substrate AIMP2; VPS35 co-immunoprecipitates with AIMP2 and Lamp2a; D620N mutation disrupts VPS35–AIMP2 and VPS35–Lamp2a interactions; VPS35 overexpression prevents AIMP2-induced PARP1-dependent cell death; VPS35 knockdown causes AIMP2-dependent PARP1 activation and cell death. Co-immunoprecipitation, siRNA knockdown, VPS35 overexpression, PARP1 activation and cell death assays Cell death & disease Medium 28383562
2017 VPS35 D620N mutation causes defects in complex I (and II) enzymatic activity and mitochondrial respiratory chain assembly (assembled complexes and supercomplexes reduced) in patient fibroblasts; these deficits are rescued by inhibition of mitochondrial fission, linking excessive fission downstream of D620N to bioenergetic impairment. Complex I/II enzymatic activity assay, Blue Native PAGE for assembled complexes, Seahorse respirometry, fission inhibitor rescue in patient fibroblasts Biochimica et biophysica acta. Molecular basis of disease Medium 28765075
2018 VPS35 D620N knock-in mutation strikingly elevates LRRK2-mediated phosphorylation of Rab8A, Rab10, and Rab12 in mouse embryonic fibroblasts and in vivo mouse tissues; LRRK2-mediated Rab10 phosphorylation is increased in neutrophils and monocytes from D620N PD patients versus controls; VPS35 knockout/knockdown suppresses LRRK2-mediated Rab phosphorylation in wild-type, LRRK2[R1441C], and VPS35[D620N] cells, indicating VPS35 controls LRRK2 kinase activity. Knock-in mouse model, phospho-Rab ELISA and Western blot, patient-derived neutrophil/monocyte analysis, VPS35 siRNA/knockout in multiple cell lines The Biochemical journal High 29743203
2018 Parkin directly ubiquitinates VPS35 via attachment of an atypical poly-ubiquitin chain to three C-terminal lysine residues; familial parkin mutations impair VPS35 ubiquitination; ubiquitination does not promote proteasomal degradation of VPS35; parkin knockdown in cortical neurons selectively disrupts vesicular sorting of ATG9A (a WASH-dependent retromer cargo); WASH complex components are markedly decreased in brains of parkin knockout mice. Co-immunoprecipitation, ubiquitination assay, mass spectrometry identification of ubiquitinated lysines, parkin KO mouse brain analysis, ATG9A trafficking assay Human molecular genetics High 29893854
2018 VPS35 dysfunction (D620N or siRNA knockdown) impairs retromer-mediated DMT1 (divalent metal transporter 1) trafficking to the trans-Golgi network, redirecting DMT1 to lysosomes and shifting intracellular iron distribution from Golgi-dominant to lysosome-enriched; treatment with retromer stabilizer R55 restores Golgi-dominant iron distribution. Fluorescent probe (Gol-SiRhoNox) for Golgi-specific Fe(II) detection combined with LysoRhoNox for lysosomal Fe(II), synchronous imaging, VPS35 dysfunction induction, R55 pharmacological rescue Chemical science Medium 30809369
2018 Loss of iPLA2-VIA (Drosophila PLA2G6 homolog) impairs retromer function by reducing interaction with Vps35 and Vps26, leading to progressive ceramide elevation and neurodegeneration; similar defects are observed upon loss of vps26 or vps35, or overexpression of α-synuclein. Co-immunoprecipitation, genetic epistasis in Drosophila, lipidomic analysis, ceramide-reducing drug rescue Cell metabolism Medium 29909971
2019 VPS35 regulates tau phosphorylation through cathepsin D availability; VPS35 overexpression reduces pathological tau in neuronal cells; VPS35 silencing causes tau accumulation; mechanistically, VPS35 controls the availability of active cathepsin D, which mediates tau degradation; VPS35 knockdown in a tauopathy mouse model exacerbates tau accumulation and motor/learning impairments. VPS35 overexpression/siRNA in neuronal cells, cathepsin D activity assay, tau phosphorylation Western blot, tauopathy mouse model with AAV-mediated VPS35 knockdown Molecular psychiatry Medium 31289348
2019 In Arabidopsis, VPS35 interaction with the RAB7 homolog RABG3f-GTP acts as a checkpoint controlling HOPS complex assembly and fusion of late endosomal compartments with the vacuole; the synthetic molecule Endosidin17 targets VPS35 and prevents this interaction, blocking retromer endosome anchoring. Multiple target identification techniques, genetic analysis, co-immunoprecipitation, chemical biology with Endosidin17 Proceedings of the National Academy of Sciences of the United States of America Low 31570580
2020 Vps35 deficiency in pyramidal neurons increases sortilin1 (Sort1) in lysosomes and causes lysosomal dysfunction; suppression of Sort1 diminishes Vps35-KO-induced dendritic defects; lysosomal Sort1 expression recapitulates Vps35-KO phenotypes, identifying Sort1 as a key cargo whose missorting to lysosomes mediates neurodegenerative pathology. Conditional Vps35 KO, Sort1 immunofluorescence in lysosomes, Sort1 siRNA rescue, Sort1 overexpression phenocopy, lysosomal function assay Cell death and differentiation Medium 31907392
2020 Vps35 deficiency increases p35 levels and Cdk5/p35 kinase activity by impairing lysosomal degradation of p35; roscovitine (Cdk5 inhibitor) reduces hyperphosphorylated tau induced by Vps35 deficiency; Cdk5/p35 acts as a VPS35 cargo, co-immunoprecipitating with VPS35. Co-immunoprecipitation, p35/Cdk5 Western blot, roscovitine pharmacological rescue, lysosome marker co-localization, tau phosphorylation assay in retinal ganglion cells Investigative ophthalmology & visual science Medium 31995153
2020 VPS35 D620N mutation in iPSC-derived neurons causes decreased autophagic flux, reduced lysosomal mass, α-synuclein accumulation, mitochondrial dysfunction (reduced membrane potential, impaired respiration, increased ROS), and defective mitophagy. iPSC reprogramming from D620N patient, dopaminergic neuron differentiation, autophagy flux assay, lysosomal staining, mitochondrial respiration (Seahorse), ROS measurement, mitophagy assay Movement disorders Medium 33142012
2021 VPS35 D620N mutant reduces mitochondrial membrane potential at steady state, desensitizes mitochondria to CCCP-induced potential collapse, inhibits PINK1 accumulation at the outer mitochondrial membrane, and consequently impairs Parkin recruitment and PINK1/Parkin-dependent mitophagy initiation. CRISPR-Cas9 heterozygous D620N knock-in in SH-SY5Y cells, CCCP treatment, mitochondrial membrane potential assay (JC-1), PINK1/Parkin localization by immunofluorescence, mitophagy assessment Translational neurodegeneration Medium 34127073
2021 VPS35 D620N knock-in mice at 14 months recapitulate cardinal PD features including progressive motor deficits, DA and metabolite changes in striatum, nigrostriatal neuron degeneration, neuroinflammation, and α-synuclein accumulation; mechanistically, D620N induces mitochondrial fragmentation and dysfunction through enhanced VPS35–DLP1 interaction and increased DLP1 complex turnover in vivo. VPS35 D620N knock-in mouse model, aging cohort analysis, motor behavior, immunohistochemistry, DA HPLC, mitochondrial morphology, Co-IP for VPS35–DLP1 in aged mice Aging cell High 33745227
2021 The Vps35 D620N variant reduces the capacity of retromer to form endosome transport carriers; Vps35 D620N cells show impaired CI-M6PR endosome-to-TGN transport due to reduced binding to the WASH complex and SNX3 (both required for transport carrier formation); endosomes are smaller and rounder with fewer tubular branches. Vps35 D620N rescue cell model (retromer KO background), CI-M6PR trafficking assay, endosome morphology analysis (electron microscopy/confocal), Co-IP for WASH and SNX3 Traffic (Copenhagen, Denmark) Medium 33347683
2022 Upon specific mtDNA damage, VPS35 mediates maturation of early endosomes to late autophagy vesicles where mitochondrial nucleoids are degraded; the ATAD3–SAMM50 axis controls nucleoid release from mitochondria, with SAMM50 acting as a gatekeeper for BAK clustering and nucleoid transfer to endosomes; this defines a non-canonical endosomal-mitophagy pathway for selective mtDNA turnover. Proximity labeling with Twinkle (nucleoid marker), VPS35 knockdown, ATAD3/SAMM50 genetic perturbation, lysosomal inhibition, ATG5 knockout, mtDNA copy number analysis, rapamycin treatment in mouse model Nature communications Medium 36344526
2023 VPS35 D620N mutation alters expression of ~220 lysosomal proteins and drives LRRK2-mediated phosphorylation of Rab proteins at the lysosome, recruiting the phospho-Rab effector RILPL1 to the lysosome where it binds the lysosomal integral membrane protein TMEM55B; D620N reduces RILPL1 levels in a manner reversed by LRRK2 inhibition and proteasome inhibitors; RILPL1 knockout enhances Rab substrate phosphorylation; TMEM55B knockout increases RILPL1 levels. Quantitative lysosomal proteomics, phospho-Rab Western blot, Co-IP of RILPL1-TMEM55B, mutagenesis of interaction interface, LRRK2 inhibitor treatment, RILPL1/TMEM55B knockout mice Science advances High 38091401
2023 VPS35 selectively binds endocytosed EGFR in early endosomes and recycles it to the cell surface, activating downstream ERK1/2 signaling; VPS35 promotes gastric cancer cell proliferation through EGFR recycling; high VPS35 expression increases sensitivity to EGFR inhibitors in xenograft and organoid models. Co-immunoprecipitation, biotin surface assay, EGFR recycling assay, ERK1/2 phosphorylation Western blot, patient-derived xenograft and organoid models EBioMedicine Medium 36738481
2023 LRRK2 kinase inhibition (MLi-2) normalizes striatal dopamine transporter (DAT) expression and function, and abolishes amphetamine-induced hyperlocomotion in VPS35 D620N knock-in mice, but not in VPS35 haploinsufficient mice; D620N elevates LRRK2-mediated phosphorylation of Rab10, Rab12, and Rab29, while haploinsufficiency reduces Rab12 phosphorylation, demonstrating VPS35 and LRRK2 functionally interact to regulate DAT function and dopamine transmission. VPS35 D620N knock-in and haploinsufficient mice, LRRK2 kinase inhibitor (MLi-2) treatment, phospho-Rab Western blot, fast-scan cyclic voltammetry, behavioral locomotion assay NPJ Parkinson's disease Medium 38110354

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. American journal of human genetics 703 21763483
2011 VPS35 mutations in Parkinson disease. American journal of human genetics 687 21763482
2014 Mutation in VPS35 associated with Parkinson's disease impairs WASH complex association and inhibits autophagy. Nature communications 369 24819384
1997 Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30, and VPS35 gene products. The Journal of cell biology 354 9105038
2015 Parkinson's disease-associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes. Nature medicine 267 26618722
2010 Vps35 mediates vesicle transport between the mitochondria and peroxisomes. Current biology : CB 247 20619655
2011 VPS35 haploinsufficiency increases Alzheimer's disease neuropathology. The Journal of cell biology 217 22105352
2015 VPS35 in Dopamine Neurons Is Required for Endosome-to-Golgi Retrieval of Lamp2a, a Receptor of Chaperone-Mediated Autophagy That Is Critical for α-Synuclein Degradation and Prevention of Pathogenesis of Parkinson's Disease. The Journal of neuroscience : the official journal of the Society for Neuroscience 212 26203154
2015 VPS35 Deficiency or Mutation Causes Dopaminergic Neuronal Loss by Impairing Mitochondrial Fusion and Function. Cell reports 211 26321632
2012 Recruitment of the endosomal WASH complex is mediated by the extended 'tail' of Fam21 binding to the retromer protein Vps35. The Biochemical journal 190 22070227
2013 The Vps35 D620N mutation linked to Parkinson's disease disrupts the cargo sorting function of retromer. Traffic (Copenhagen, Denmark) 180 24152121
2018 The Parkinson's disease VPS35[D620N] mutation enhances LRRK2-mediated Rab protein phosphorylation in mouse and human. The Biochemical journal 166 29743203
2014 VPS35 dysfunction impairs lysosomal degradation of α-synuclein and exacerbates neurotoxicity in a Drosophila model of Parkinson's disease. Neurobiology of disease 157 25107340
2018 Genotype-phenotype relations for the Parkinson's disease genes SNCA, LRRK2, VPS35: MDSGene systematic review. Movement disorders : official journal of the Movement Disorder Society 155 30357936
2014 Retromer binding to FAM21 and the WASH complex is perturbed by the Parkinson disease-linked VPS35(D620N) mutation. Current biology : CB 151 24980502
2018 Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain. Cell metabolism 146 29909971
2014 Parkinson's disease genes VPS35 and EIF4G1 interact genetically and converge on α-synuclein. Neuron 143 25533483
2006 The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain. Nature structural & molecular biology 143 16732284
2017 VPS35, the Retromer Complex and Parkinson's Disease. Journal of Parkinson's disease 142 28222538
2014 Parkinson's disease-linked mutations in VPS35 induce dopaminergic neurodegeneration. Human molecular genetics 129 24740878
2014 Retromer-dependent neurotransmitter receptor trafficking to synapses is altered by the Parkinson's disease VPS35 mutation p.D620N. Human molecular genetics 116 25416282
1992 Alternative pathways for the sorting of soluble vacuolar proteins in yeast: a vps35 null mutant missorts and secretes only a subset of vacuolar hydrolases. Molecular biology of the cell 98 1498362
2017 Vps35 in cooperation with LRRK2 regulates synaptic vesicle endocytosis through the endosomal pathway in Drosophila. Human molecular genetics 93 28482024
2019 Parkinson's disease-linked D620N VPS35 knockin mice manifest tau neuropathology and dopaminergic neurodegeneration. Proceedings of the National Academy of Sciences of the United States of America 91 30842285
2012 A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants. Journal of medical genetics 80 23125461
2014 Vacuolar protein sorting 35 (Vps35) rescues locomotor deficits and shortened lifespan in Drosophila expressing a Parkinson's disease mutant of Leucine-Rich Repeat Kinase 2 (LRRK2). Molecular neurodegeneration 79 24915984
2007 Drosophila Vps35 function is necessary for normal endocytic trafficking and actin cytoskeleton organisation. Journal of cell science 75 18057029
2022 Mitochondrial membrane proteins and VPS35 orchestrate selective removal of mtDNA. Nature communications 74 36344526
2013 The VPS35 gene and Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society 74 23536430
2012 Frequency of the D620N mutation in VPS35 in Parkinson disease. Archives of neurology 73 22801713
2016 Parkinson Disease-linked Vps35 R524W Mutation Impairs the Endosomal Association of Retromer and Induces α-Synuclein Aggregation. The Journal of biological chemistry 72 27385586
2012 VPS35 mutation in Japanese patients with typical Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society 71 22991136
2015 VPS35-deficiency results in an impaired AMPA receptor trafficking and decreased dendritic spine maturation. Molecular brain 68 26521016
2014 Molecular insights into Rab7-mediated endosomal recruitment of core retromer: deciphering the role of Vps26 and Vps35. Traffic (Copenhagen, Denmark) 68 25367362
2018 Increased Microglial Activity, Impaired Adult Hippocampal Neurogenesis, and Depressive-like Behavior in Microglial VPS35-Depleted Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 66 29853629
2018 Altered dopamine release and monoamine transporters in Vps35 p.D620N knock-in mice. NPJ Parkinson's disease 65 30155515
2016 Vps35-dependent recycling of Trem2 regulates microglial function. Traffic (Copenhagen, Denmark) 64 27717139
2015 VPS35 pathogenic mutations confer no dominant toxicity but partial loss of function in Drosophila and genetically interact with parkin. Human molecular genetics 62 26251041
2012 VPS35 regulates developing mouse hippocampal neuronal morphogenesis by promoting retrograde trafficking of BACE1. Biology open 61 23259059
2018 A Golgi-targeting fluorescent probe for labile Fe(ii) to reveal an abnormal cellular iron distribution induced by dysfunction of VPS35. Chemical science 59 30809369
2018 Parkin mediates the ubiquitination of VPS35 and modulates retromer-dependent endosomal sorting. Human molecular genetics 58 29893854
2016 Impaired striatal dopamine release in homozygous Vps35 D620N knock-in mice. Human molecular genetics 57 28173004
2013 Whole exome sequencing of rare variants in EIF4G1 and VPS35 in Parkinson disease. Neurology 53 23408866
2011 Screening for VPS35 mutations in Parkinson's disease. Neurobiology of aging 51 22154191
2010 Implication of mouse Vps26b-Vps29-Vps35 retromer complex in sortilin trafficking. Biochemical and biophysical research communications 51 21040701
2021 Parkinson's disease-associated VPS35 mutant reduces mitochondrial membrane potential and impairs PINK1/Parkin-mediated mitophagy. Translational neurodegeneration 49 34127073
2020 The Role of VPS35 in the Pathobiology of Parkinson's Disease. Cellular and molecular neurobiology 49 32323152
2016 VPS35 binds farnesylated N-Ras in the cytosol to regulate N-Ras trafficking. The Journal of cell biology 47 27502489
2020 Vps35 Deficiency Impairs Cdk5/p35 Degradation and Promotes the Hyperphosphorylation of Tau Protein in Retinal Ganglion Cells. Investigative ophthalmology & visual science 46 31995153
2020 Mitochondrial and Clearance Impairment in p.D620N VPS35 Patient-Derived Neurons. Movement disorders : official journal of the Movement Disorder Society 44 33142012
2017 Parkinson's disease-associated pathogenic VPS35 mutation causes complex I deficits. Biochimica et biophysica acta. Molecular basis of disease 43 28765075
2019 Contributions of VPS35 Mutations to Parkinson's Disease. Neuroscience 42 30660673
2020 (D620N) VPS35 causes the impairment of Wnt/β-catenin signaling cascade and mitochondrial dysfunction in a PARK17 knockin mouse model. Cell death & disease 41 33257649
2014 VPS35 Parkinson's disease phenotype resembles the sporadic disease. Journal of neural transmission (Vienna, Austria : 1996) 41 24557499
2013 Vps35 loss promotes hyperresorptive osteoclastogenesis and osteoporosis via sustained RANKL signaling. The Journal of cell biology 41 23509071
2016 VPS35 regulates cell surface recycling and signaling of dopamine receptor D1. Neurobiology of aging 39 27460146
2020 Coupling of terminal differentiation deficit with neurodegenerative pathology in Vps35-deficient pyramidal neurons. Cell death and differentiation 38 31907392
2017 A conserved retromer sorting motif is essential for mitochondrial DLP1 recycling by VPS35 in Parkinson's disease model. Human molecular genetics 38 28040727
2019 VPS35 regulates tau phosphorylation and neuropathology in tauopathy. Molecular psychiatry 36 31289348
2022 Microglial VPS35 deficiency impairs Aβ phagocytosis and Aβ-induced disease-associated microglia, and enhances Aβ associated pathology. Journal of neuroinflammation 34 35236374
2020 DNA and RNA sequencing identified a novel oncogene VPS35 in liver hepatocellular carcinoma. Oncogene 34 32071398
2022 Understanding the contributions of VPS35 and the retromer in neurodegenerative disease. Neurobiology of disease 33 35588987
2014 In vivo evidence of pathogenicity of VPS35 mutations in the Drosophila. Molecular brain 33 25288323
2023 Parkinson's VPS35[D620N] mutation induces LRRK2-mediated lysosomal association of RILPL1 and TMEM55B. Science advances 32 38091401
2021 VPS35 D620N knockin mice recapitulate cardinal features of Parkinson's disease. Aging cell 32 33745227
2021 KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway. Cell & bioscience 32 33858520
2015 VPS29-VPS35 intermediate of retromer is stable and may be involved in the retromer complex assembly process. FEBS letters 32 25937119
2023 VPS35 promotes cell proliferation via EGFR recycling and enhances EGFR inhibitors response in gastric cancer. EBioMedicine 31 36738481
2023 VPS35 promotes gastric cancer progression through integrin/FAK/SRC signalling-mediated IL-6/STAT3 pathway activation in a YAP-dependent manner. Oncogene 31 37950040
2013 Pathogenic mutation in VPS35 impairs its protection against MPP(+) cytotoxicity. International journal of biological sciences 31 23411763
2020 VPS35 and the mitochondria: Connecting the dots in Parkinson's disease pathophysiology. Neurobiology of disease 30 32853677
2019 Interaction between VPS35 and RABG3f is necessary as a checkpoint to control fusion of late compartments with the vacuole. Proceedings of the National Academy of Sciences of the United States of America 30 31570580
2007 The vacuolar-ATPase inhibitor bafilomycin and mutant VPS35 inhibit canonical Wnt signaling. Neurobiology of disease 30 17239604
2007 Dominant-negative behavior of mammalian Vps35 in yeast requires a conserved PRLYL motif involved in retromer assembly. Traffic (Copenhagen, Denmark) 29 17916227
2014 VPS35 and DNAJC13 disease-causing variants in essential tremor. European journal of human genetics : EJHG 26 25118025
2017 Identification of VPS35 p.D620N mutation-related Parkinson's disease in a Taiwanese family with successful bilateral subthalamic nucleus deep brain stimulation: a case report and literature review. BMC neurology 25 28985717
2016 Role of the VPS35 D620N mutation in Parkinson's disease. Parkinsonism & related disorders 25 27964832
2012 VPS35 Asp620Asn and EIF4G1 Arg1205His mutations are rare in Parkinson disease from southwest China. Neurobiology of aging 25 23261770
2023 Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson's disease. NPJ Parkinson's disease 24 37015928
2020 Ependymal Vps35 Promotes Ependymal Cell Differentiation and Survival, Suppresses Microglial Activation, and Prevents Neonatal Hydrocephalus. The Journal of neuroscience : the official journal of the Society for Neuroscience 24 32291328
2013 EIF4G1 R1205H and VPS35 D620N mutations are rare in Parkinson's disease from South Africa. Neurobiology of aging 24 24080171
2021 Formation of retromer transport carriers is disrupted by the Parkinson disease-linked Vps35 D620N variant. Traffic (Copenhagen, Denmark) 22 33347683
2019 Microglial VPS35 deficiency regulates microglial polarization and decreases ischemic stroke-induced damage in the cortex. Journal of neuroinflammation 22 31771656
2019 VPS35-Based Approach: A Potential Innovative Treatment in Parkinson's Disease. Frontiers in neurology 22 31920908
2017 VPS35 regulates parkin substrate AIMP2 toxicity by facilitating lysosomal clearance of AIMP2. Cell death & disease 22 28383562
2021 Neuronal VPS35 deletion induces spinal cord motor neuron degeneration and early post-natal lethality. Brain communications 21 34704029
2020 Endosomal dysfunction in iPSC-derived neural cells from Parkinson's disease patients with VPS35 D620N. Molecular brain 21 33032646
2014 Vps35 haploinsufficiency results in degenerative-like deficit in mouse retinal ganglion neurons and impairment of optic nerve injury-induced gliosis. Molecular brain 21 24512632
2013 VPS35 and EIF4G1 mutations are rare in Parkinson's disease among Indians. Neurobiology of aging 21 23726718
2023 Inhibition of LRRK2 kinase activity rescues deficits in striatal dopamine physiology in VPS35 p.D620N knock-in mice. NPJ Parkinson's disease 20 38110354
2021 Impaired neurogenesis in the hippocampus of an adult VPS35 mutant mouse model of Parkinson's disease through interaction with APP. Neurobiology of disease 20 33636388
2012 Contribution of VPS35 genetic variability to LBD in the Flanders-Belgian population. Neurobiology of aging 20 22336192
1996 Genetic mapping and embryonic expression of a novel, maternally transcribed gene Mem3. Mammalian genome : official journal of the International Mammalian Genome Society 19 8678978
2024 Intermittent hypoxia training enhances Aβ endocytosis by plaque associated microglia via VPS35-dependent TREM2 recycling in murine Alzheimer's disease. Alzheimer's research & therapy 18 38831312
2021 Mechanisms of VPS35-Mediated Neurodegeneration in Parkinson's Disease. International review of movement disorders 17 35497708
2020 Altered striatal dopamine levels in Parkinson's disease VPS35 D620N mutant transgenic aged mice. Molecular brain 17 33261640
2018 VPS35 depletion does not impair presynaptic structure and function. Scientific reports 17 29445238
2016 Autosomal dominant Parkinson's disease: Incidence of mutations in LRRK2, SNCA, VPS35 and GBA genes in Brazil. Neuroscience letters 17 27777137
2024 VPS35 and retromer dysfunction in Parkinson's disease. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 16 38368930
2020 Depletion of VPS35 attenuates metastasis of hepatocellular carcinoma by restraining the Wnt/PCP signaling pathway. Genes & diseases 16 33997170

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