| 1997 |
VPS29 (yeast ortholog) is required for endosome-to-Golgi retrieval of the vacuolar sorting receptor Vps10p; loss of VPS29 causes Vps10p to mislocalize from the Golgi to the vacuolar membrane, and Vps35p continues to cofractionate with Vps10p in vps29 mutants, indicating VPS29 acts upstream of Vps35p-Vps10p interaction in the retrieval pathway. |
Genetic loss-of-function (vps29 mutant), subcellular fractionation, epistasis analysis in S. cerevisiae |
The Journal of cell biology |
High |
9105038
|
| 2005 |
Crystal structure of mammalian VPS29 reveals a phosphoesterase fold with structural similarity to divalent metal-containing phosphoesterases, but no detectable phosphoesterase activity in vitro; VPS29 and VPS26 bind independently to VPS35 to form a high-affinity heterotrimeric subcomplex; mutagenesis of the VPS35-binding surface on VPS29 disrupts endosomal membrane association in vivo; a conserved hydrophobic surface distinct from the VPS35-binding site mediates assembly with sorting nexins in yeast. |
X-ray crystallography, in vitro binding assays, site-directed mutagenesis, in vivo localization |
Nature structural & molecular biology |
High |
15965486
|
| 2006 |
Human VPS29 displays in vitro phosphatase activity toward a serine-phosphorylated peptide from the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor (CI-M6PR); efficient dephosphorylation requires co-presence of hVPS26 and hVPS35; VPS29 phosphatase activity depends on zinc coordination at active-site residues and is abolished by alanine substitution of metal-coordinating residues or zinc chelation. |
In vitro phosphatase assay with recombinant proteins, inductively coupled plasma MS for zinc binding, active-site mutagenesis |
The Biochemical journal |
Medium |
16737443
|
| 2011 |
VPS29 is not a functional metalloenzyme; X-ray crystallography and NMR show VPS29 can coordinate Mn2+ and Zn2+ but with low affinity; phosphatase assays confirm no activity toward peptide substrates; NMR RDC measurements demonstrate VPS29 is a rigid scaffold; NMR chemical shift mapping shows VPS29 associates with SNX1 via a conserved hydrophobic surface with low affinity, requiring additional interactions for stable complex formation in vivo. |
X-ray crystallography, NMR spectroscopy (RDC, chemical shift mapping), ITC, phosphatase assays |
PloS one |
High |
21629666
|
| 2010 |
The VPS26b-VPS29-VPS35 retromer complex mediates transport of sortilin from endosomes to the trans-Golgi network; loss of VPS26b destabilizes VPS35 protein and eliminates the VPS26b-VPS29-VPS35 complex while the VPS26a-VPS29-VPS35 complex remains intact; VPS26b knockout results in ~20% increase in sortilin levels. |
VPS26b knockout mouse, Co-IP, Western blot, protein level quantification |
Biochemical and biophysical research communications |
Medium |
21040701
|
| 2015 |
VPS29 and VPS35 form a biologically stable subcomplex in vivo; deficiency of VPS35 or VPS29 causes degradation of other retromer subunits, whereas VPS26 deficiency does not affect VPS29 or VPS35 levels; the VPS29-VPS35 subcomplex is more resistant to ubiquitin-proteasome-dependent degradation than the VPS26-VPS35 subcomplex. |
siRNA knockdown/KO, in vitro binding assays, ubiquitin-proteasome inhibitor treatment, Western blot |
FEBS letters |
Medium |
25937119
|
| 2017 |
The Legionella pneumophila effector protein RidL binds the VPS29 retromer subunit via a protruding β-hairpin; the β-hairpin Ile170 in RidL and Leu152 in VPS29 are critical for the interaction; RidL binding displaces the Rab7 GTPase-activating protein TBC1D5 from VPS29 and from Legionella-containing vacuoles, thereby blocking retrograde vesicle trafficking. |
X-ray crystallography of RidL-VPS29 complex, site-directed mutagenesis, Co-IP in eukaryotic cells, in vitro binding assays |
Nature communications |
High |
29146912
|
| 2020 |
VPS29 is required for retromer localization to neuropil; in Drosophila Vps29 mutants, VPS35 and VPS26 are normally expressed and associated but retromer is mislocalized from neuropil to soma with the Rab7 GTPase; Vps29 phenotypes (synaptic transmission defects, locomotion, survival) are suppressed by reducing Rab7 or overexpressing TBC1D5 (a Rab7 GAP), placing VPS29 upstream of Rab7 regulation in retromer localization. |
Drosophila Vps29 KO, genetic epistasis (Rab7 reduction, TBC1D5 overexpression), co-immunoprecipitation, immunofluorescence, behavioral assays, ultrastructural analysis |
eLife |
High |
32286230
|
| 2020 |
VARP binds VPS29 via a 12-residue four-cysteine Zn-fingernail motif (two present in VARP); NMR/X-ray structure of the VPS29:VARP Zn-fingernail complex shows VARP and TBC1D5 bind the same site on VPS29 and compete for VPS29 binding in vivo; mutations abolishing VPS29:VARP binding inhibit trafficking from endosomes to the cell surface; assembled retromer arches (hetero-hexameric, membrane-attached) favor VARP binding through simultaneous engagement of two VPS29 subunits. |
NMR and X-ray crystallography of VPS29:VARP complex, site-directed mutagenesis, competition binding assays, trafficking assays in cells |
Nature communications |
High |
33024112
|
| 2022 |
VPS29 deficiency alters endosome morphology and acidity and attenuates endosomal protease activity, causing entrapment of incoming coronaviruses (HCoV-OC43, SARS-CoV-2, including Omicron variant, ebolavirus) in endosomes and blocking infection; VPS29 loss enhances influenza A virus infection, demonstrating opposing roles in endocytic viral entry depending on the virus. |
Genome-wide CRISPR loss-of-function screen, VPS29 KO validation, endosome morphology/acidity assays, viral infection assays |
mBio |
Medium |
35229640
|
| 2024 |
FAM21 (WASH complex subunit) contains a peptide fragment that directly binds VPS29; crystal structure of VPS29 bound to FAM21-derived peptide shows a distinctive sharp bend inserting into a conserved hydrophobic pocket on VPS29, using the same binding mode as other VPS29 effectors; this interaction is distinct from FAM21's two binding sites on VPS35. |
X-ray crystallography of VPS29:FAM21 peptide complex, in vitro binding assays, mutagenesis |
Protein science |
High |
38607248
|
| 2025 |
A third VPS29 isoform (VPS29C) harbors an extended N-terminal sequence that acts as an autoinhibitory sequence blocking access to the hydrophobic groove required for effector protein recruitment to Retromer and for association with Retriever and Commander complexes; VPS29C uncouples Retromer-dependent cargo sorting from broader regulatory roles of VPS29 in the endosomal-lysosomal network. |
AlphaFold predictive modeling, in vitro complex reconstitution, mass spectrometry, molecular cell biology |
Proceedings of the National Academy of Sciences of the United States of America |
High |
40587794
|
| 2013 |
In C. elegans, partial disruption of the retromer cargo-selective subcomplex (including VPS29 ortholog) causes Wls (Wnt sorting receptor) to be routed for lysosomal degradation; inhibition of late endosomal maturation restores Wnt secretion by facilitating SNX-BAR-dependent Wls retrieval, placing VPS29-containing retromer at the step of sorting Wls at early/late endosome boundary. |
C. elegans genetic loss-of-function, epistasis with late endosome maturation mutants, fluorescence microscopy of Wls trafficking |
Cellular signalling |
Medium |
24056045
|
| 2024 |
ATG5 associates with retromer core components VPS26, VPS29, and VPS35; knockout of ATG5 blocks trafficking of GLUT1 to the plasma membrane; other genes essential for membrane atg8ylation also affect GLUT1 sorting, indicating that membrane atg8ylation regulates retromer function in endosomal sorting independently of canonical autophagy. |
Co-IP, ATG5 KO, GLUT1 trafficking assay, genetic knockout of atg8ylation pathway components |
bioRxivpreprint |
Low |
|