| 2017 |
WDR81 interacts with the autophagy cargo receptor p62 (SQSTM1) and facilitates recognition of ubiquitinated proteins by p62. WDR81 also interacts with LC3C through canonical LIR (LC3-interacting region) motifs located in the BEACH domain, promoting LC3C recruitment to ubiquitinated protein aggregates. Loss of WDR81 causes accumulation of ubiquitinated proteins and p62 bodies, and WDR81 inactivation in mice causes accumulation of p62 bodies in cortical and striatal neurons. |
Co-immunoprecipitation, loss-of-function (KO mice, cell-based), LIR motif mutagenesis, immunofluorescence, mouse brain histology |
The Journal of cell biology |
High |
28404643
|
| 2017 |
WDR81 mutations in patients and Drosophila WDR81 ortholog knockdown both result in increased mitotic index and delayed prometaphase/metaphase transition in neural progenitor/stem cells, indicating a conserved role for WDR81 in mitotic progression. |
Patient fibroblast analysis (mitotic index measurement), Drosophila RNAi knockdown of WDR81 ortholog in neural stem cells, whole-exome sequencing of patients |
Brain : a journal of neurology |
Medium |
28969387
|
| 2016 |
WDR81 functions in a complex with WDR91 to regulate endolysosomal trafficking. Loss of WDR81 results in swollen endolysosomal compartments (enlarged early and late endosomes), reduced delivery of endocytosed cargo to cathepsin-active lysosomes, and impaired degradation of tetherin (BST2) and EGF-stimulated EGFR. The WDR81-WDR91 complex is required for fusion of endolysosomal compartments. |
Forward genetic screen (haploid KBM7 cells), KO cell lines, endosomal morphology analysis, receptor degradation assays, dextran trafficking to lysosomes |
Traffic (Copenhagen, Denmark) |
High |
27126989
|
| 2018 |
WDR81 suppresses endosomal PtdIns3P (PI3P) synthesis, likely by inhibiting assembly of the class III PI3K complex. In the absence of WDR81, elevated endosomal PtdIns3P leads to retention of the PtdIns3P-binding protein SARA on endosomes and hyperactivation of SARA-dependent TGFβ signaling, impairing adult hippocampal neurogenesis. Inhibition of PI3K-III or suppression of SARA-dependent TGFβ signaling rescues the neurogenesis defect in WDR81-deficient mice. |
WDR81 KO in adult neural progenitor cells (conditional ablation in mice), PtdIns3P measurement, SARA localization analysis, epistasis by PI3K-III inhibitor and TGFβ pathway inhibition, behavioral testing (hippocampus-dependent learning) |
Molecular psychiatry |
High |
30531936
|
| 2013 |
A missense mutation L1349P in the predicted major facilitator superfamily (MFS) domain of WDR81 causes Purkinje cell degeneration and photoreceptor cell loss in mice. WDR81 localizes to mitochondria in Purkinje cell neurons (shown by immunoelectron microscopy and mitochondrial-enriched fractionation), and mutant Purkinje cell dendrites display aberrant large spheroid-like mitochondria. |
ENU mutant mouse characterization, transgenic rescue, immunoelectron microscopy, subcellular fractionation (mitochondria-enriched fractions), electron microscopy |
The Journal of neuroscience : the official journal of the Society for Neuroscience |
Medium |
23595742
|
| 2021 |
WDR81's BEACH and MFS domains are sufficient for its recruitment to Huntingtin polyQ aggregates. The WD40 repeat domain of WDR81 is essential for interaction with the covalently bound ATG5-ATG12 conjugate. WDR81 facilitates recruitment of autophagic proteins onto polyQ aggregates and promotes autophagic clearance. In C. elegans, deletion of the WDR81 homolog SORF-2 causes p62 body accumulation and exacerbates α-synuclein-induced neuron loss; overexpression of SORF-2 or human WDR81 restores neuron viability. |
Domain deletion/mutagenesis, Co-immunoprecipitation (WDR81 with ATG5-ATG12), C. elegans loss-of-function and overexpression, fibroblasts from HD patients, primary neuron viability assays |
PLoS genetics |
High |
33730050
|
| 2022 |
WDR81 is required for the endosomal maturation step that allows late-penetrating viruses (reovirus, VSV-EBO GP) to transit through late endosomes. WDR81 KO does not affect viral attachment or uptake into early endosomes, but causes accumulation of viral particles in dead-end compartments and impairs viral gene expression and infectious particle production. Human WDR81 complements mouse WDR81 KO cells, confirming functional conservation. |
CRISPR-Cas9 KO screen (>20,000 genes), complementation with human WDR81, viral infection assays (reovirus, VSV, VSV-EBO GP), endosomal trafficking analysis |
PLoS pathogens |
High |
35320319
|
| 2025 |
WDR81 represses IKK complex-mediated activation of NFκB pro-survival gene expression. In WDR81-deficient cells, expression of several pro-survival genes is upregulated via the IKK-NFκB pathway. Blocking IKK signaling in WDR81-deficient cells restores pro-survival gene expression to normal levels and re-sensitizes cells to apoptosis triggers, revealing a link between endosomally localized WDR81 and IKK-NFκB signaling. |
WDR81 KO cells, gene expression analysis, IKK inhibitor epistasis, apoptosis assays with multiple agonists |
mBio |
Medium |
41042063
|
| 2021 |
WDR81 gene silencing in U87-MG glioblastoma cells reduces exosome secretion (concentration and protein/RNA content), consistent with WDR81 acting as a negative regulator of class III PI3K activity whose loss normally suppresses autophagy and increases exosome production. |
siRNA knockdown, real-time qRT-PCR, exosome isolation and quantification (DLS, protein/RNA content measurement), MTT viability assay |
Journal of molecular neuroscience : MN |
Low |
33954857
|
| 2025 |
WDR81 contains a conserved TBM (TMEM55B Binding Motif) and co-immunoprecipitates with TMEM55B, a lysosomal membrane protein, in a phospho-Rab-independent manner, placing WDR81 within a lysosomal adaptor complex centered on TMEM55B. |
Co-immunoprecipitation, mutational analysis of TBM motif, crystal structure of TMEM55B-RILPL1 complex as reference |
bioRxiv (preprint)preprint |
Low |
bio_10.1101_2025.08.19.670962
|