| 2006 |
WDFY2 localizes to a subset of early endosomes residing within 100 nm from the plasma membrane that are positive for transferrin but lack classical markers Rab5 and EEA1; RNAi silencing of WDFY2 in both C. elegans and mammalian cells impairs transferrin endocytosis, establishing a required role in early endocytic processing. |
RNAi screen in C. elegans, siRNA knockdown in mammalian cells, quantitative fluorescence microscopy, transferrin uptake assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
16873553
|
| 2007 |
FYVE domain variation among FYVE domain-containing proteins, including WDFY2, modulates endosomal binding through differences in oligomerization propensity, membrane bilayer insertion, and electrostatic interactions — properties conferred by residues outside the PtdIns3P head-group recognition site. |
In vitro PtdIns3P binding assays, cell-based endosome localization assays with FYVE domain mutants |
Biochemical Society symposium |
Medium |
17233583
|
| 2010 |
WDFY2-positive early endosomes specifically co-localize with Akt2 but not Akt1; WDFY2 depletion selectively reduces Akt2 protein levels and impairs insulin-stimulated phosphorylation of Akt substrates, glucose transport, and adipogenic gene expression, establishing WDFY2-enriched endosomes as an isoform-specific scaffold for Akt2 signaling downstream of insulin. |
Quantitative fluorescence microscopy (co-localization), siRNA knockdown, insulin stimulation assays, phospho-substrate immunoblotting, glucose transport assay, gene expression analysis |
The Journal of biological chemistry |
High |
20189988
|
| 2017 |
WDFY2 is identified as an LKB1 regulator downstream of class III PI3K (CIII-PI3K) on endosomes; in Drosophila tissues and human organoids, the endosomal (but not autophagic) function of CIII-PI3K controls epithelial polarity through WDFY2-dependent regulation of LKB1 activity and localization. |
Genetic epistasis in Drosophila, human organoid depletion experiments, in vivo co-depletion rescue assays |
Nature cell biology |
High |
29084199
|
| 2018 |
In C. elegans, WDFY-2 levels at periciliary endosomes are controlled by the early endosome maturation factors RABS-5 (Rabenosyn-5) and VPS-45, which regulate periciliary vesicle number and ciliary membrane homeostasis including polycystin-2 (PKD-2) levels. |
C. elegans genetics, fluorescence microscopy of endosomal markers, cilia morphology assays |
The EMBO journal |
Medium |
29572244
|
| 2019 |
WDFY2 localizes to endosomal tubules via PtdIns3P binding and interacts with the v-SNARE VAMP3; WDFY2 knockout causes redistribution of VAMP3 into small vesicles near the plasma membrane, leading to increased VAMP3-dependent secretion of MT1-MMP (MMP14), enhanced extracellular matrix degradation, and increased cell invasion. |
Co-immunoprecipitation (WDFY2–VAMP3 interaction), WDFY2 knockout cells, live-cell imaging, MT1-MMP secretion assay, extracellular matrix degradation assay, Transwell invasion assay |
Nature communications |
High |
31253801
|
| 2019 |
WDFY2 deletion causes increased MMP recycling and secretion from endosomes, leading to elevated matrix degradation and cell invasion, consistent with a gatekeeper role for VAMP3-dependent MMP recycling. |
WDFY2 knockout, extracellular matrix degradation assay (commentary/summary of PMID:31253801) |
Molecular & cellular oncology |
Medium |
31692886
|
| 2019 |
p63 transcription factor isoforms (ΔN and TA) transcriptionally activate WDFY2 expression through specific p63 response elements in the WDFY2 promoter, validated in TP53-null cells and yeast-based assays, placing WDFY2 downstream of p63 in cancer regulation and limb development networks. |
Overexpression of p63 isoforms in TP53-null cells, bioinformatics identification of response elements, yeast-based transcription assay, mammalian reporter assay |
Bioscience reports |
Medium |
31789342
|
| 2020 |
WDFY2 interacts with the insulin receptor (INSR) via its WD1-4 domain and is required for endosomal localization of INSR after insulin stimulation; this ensures recruitment of IRS1/2 to endosomal INSR, enabling IRS1/2 phosphorylation and downstream Akt2 activation. Wdfy2 knockout mice display systemic insulin resistance with impaired hepatic Akt2 signaling, increased gluconeogenesis, and reduced glycogen accumulation. |
Wdfy2 knockout mice, co-immunoprecipitation (WDFY2–INSR interaction, domain mapping), endosomal fractionation, phosphorylation assays (Akt2, FoxO1, GSK-3β), glucose/glycogen metabolic assays, adeno-associated virus rescue in db/db mice |
Diabetes |
High |
32641353
|
| 2025 |
WDFY2 is phosphorylated at serine 84 by the ATM-CHK2 kinase axis in response to DNA double-strand breaks (DSBs); this phosphorylation recruits WDFY2 to DSB sites where it directly interacts with MRE11 and NBS1, bridging the MRE11-RAD50 subcomplex with NBS1 to promote MRN complex formation and DNA end resection required for homologous recombination repair. WDFY2 deficiency or the non-phosphorylatable S84A mutant impairs HR repair and reduces cell survival after DNA damage. |
In vitro kinase assay (ATM, CHK2), phosphorylation site mutagenesis (S84A), Co-immunoprecipitation (WDFY2–MRE11, WDFY2–NBS1), laser-induced DSB recruitment assay, HR repair reporter assay, cell survival assay |
Cell reports |
High |
41196680
|
| 2025 |
WDFY2 acts as a chaperone that retains VAMP3 at endosomes; phosphorylation of VAMP3 upon LPS-induced dendritic cell activation releases VAMP3 from WDFY2, enabling trafficking of IL-6-positive VAMP3-positive vesicles to the plasma membrane for IL-6 secretion. |
Quantitative TIRF microscopy, phosphoproteomic analysis, co-immunoprecipitation (WDFY2–VAMP3), VAMP3 phosphomimetic/phosphodead mutants, IL-6 secretion assay |
Journal of cell science |
Medium |
40977280
|