Ask about this productRelated genes to: WDFY3 antibody
- Gene:
- WDFY3 NIH gene
- Name:
- WD repeat and FYVE domain containing 3
- Previous symbol:
- -
- Synonyms:
- KIAA0993, ALFY, ZFYVE25
- Chromosome:
- 4q21.23
- Locus Type:
- gene with protein product
- Date approved:
- 2003-03-28
- Date modifiied:
- 2016-10-05
Related products to: WDFY3 antibody
Related articles to: WDFY3 antibody
- WDFY3/ALFY is an adaptor protein involved in selective autophagy. Loss of Wdfy3 in mice causes severe deficits in neuronal health, and pathogenic mutations in WDFY3 are associated with neurodevelopmental disorders in humans. As impaired autophagy is increasingly implicated in Parkinson's disease (PD) and other neurodegenerative disorders, we investigated whether Wdfy3 haploinsufficiency produces early molecular and cellular signatures of neurodegeneration in Wdfy3 mice, given that these diseases often exhibit presymptomatic alterations preceding overt clinical manifestations. Cortical tissue from 3-month-old presymptomatic mice showed significant proteomic overlap with both patient-derived PD cell lines and human brain proteomic datasets, particularly from the substantia nigra, underscoring the translational relevance of this model. Consistent with disease progression, immunofluorescence analyses of the cortex and substantia nigra from 14-month-old mice revealed significant dysregulation of multiple markers associated with neurodegeneration. Together, these findings demonstrate that impaired autophagy resulting from reduced Wdfy3 expression recapitulates key features of neurodegenerative disease at both early and later stages. By providing a platform to investigate presymptomatic pathogenic mechanisms, this model may inform the development and testing of future diagnostic and therapeutic strategies aimed at preserving neuronal health. - Source: PubMed
Publication date: 2026/04/04
Vorkapich AldoMustafa ArshiFlores-Torres Amanda LZarbalis Konstantinos SGiulivi Cecilia - BEACH-domain-containing proteins (BDCPs) are large scaffolding proteins that regulate vesicle trafficking, autophagy, and granule biogenesis. This review synthesizes recent mechanistic and clinical advances defining BDCP functions in hematopoietic stem and progenitor cell (HSPC) biology, immune regulation, and platelet function, highlighting relevance to human disease. - Source: PubMed
Publication date: 2026/03/17
Hateley AbigailGanuza Miguel - M1 macrophage activation is crucial in chronic inflammatory diseases, yet its molecular mechanism is unclear. - Source: PubMed
Publication date: 2026/01/27
Toriola Mubaraq ATimlin EmmaBulbule SarojiniReyes AmyAdedeji Omolola MaryGottschalk C GunnarBarua AnimeshArnold Leggy ARoy Avik - The acquired toxicity of the familial amyotrophic lateral sclerosis (ALS)-associated mutant Zn-superoxide dismutase 1 (SOD1) protein has been implicated in motoneuron death, and cytosolic aggregates or inclusions have been observed in the cytoplasm of motoneurons, astrocytes, and neuronal axons but not in that of microglia. This study elucidates the mechanisms by which mutant SOD1 does not aggregate in and is cleared by microglia. We generated pcDNA3-Venus-tagged SOD1 constructs: wild-type SOD1 and mutant SOD1 were used as controls, and the A4V, D90A, and G93A SOD1 mutants were used as disease-related constructs; these plasmids were introduced into the Ra2 microglia line for subsequent evaluation. In spinal cords collected from postsymptomatic G93A mice, very little aggregation of the mutant SOD1 protein was detected in microglia, consistent with previous reports. Our new findings, which were based on immunohistochemical, Western blot, and enzyme immunoassay analyses, revealed that the protein expression of mutant SOD1 in microglia is significantly lower than that of wild-type SOD1. Furthermore, we observed the recovery of mutant SOD1 protein levels in autophagy suppression experiments and its colocalization with WDFY3, a selective autophagy-related protein. These in vitro results demonstrate that only the mutant SOD1 protein (i.e., not wild-type SOD1) is degraded by selective autophagy. Furthermore, we found that both wild-type and mutant SOD1 are secreted directly from microglia. These findings provide an opportunity to elucidate the precise mechanism through which microglia manage mutant SOD1 proteins during the pathological process of ALS and are likely to lead to improvements in ALS treatment strategies. - Source: PubMed
Publication date: 2026/01/22
Murakami KumikoSudou NorihiroKurata AtushiKawaguchi-Niida Motoko - Efficient efferocytosis is crucial for immune homeostasis. Conversely, excessive apoptotic cell (AC) death and impaired macrophage efferocytosis lead to autoantigen release, autoantibody production, and immune activation. It is unclear whether immunogenic autoantigens from impaired clearance are the sole cause of autoimmunity or if AC efferocytosis directly alters macrophage function, affecting T cell activation and amplifying autoimmunity. Our prior work identified WDFY3 as essential for macrophage efferocytosis. Here, we demonstrate that myeloid Wdfy3 knockout exacerbates autoimmunity in young mice receiving systemic AC injections and middle-aged mice developing autoreactivity. Mechanistically, myeloid Wdfy3 deletion impairs efferocytosis, increasing autoantigen availability, and augments MHC-II-mediated antigen presentation and cytokine dysregulation, thereby promoting CD4 T cell activation. In contrast, WDFY3 overexpression enhances efferocytosis, suppresses macrophage-mediated CD4 T cell activation, and mitigates autoimmunity. Thus, macrophage WDFY3 functions as a protective factor against autoimmunity. Enhancing macrophage efferocytosis and reprogramming macrophage responses to ACs may represent promising strategies to limit autoimmune disorders and age-associated autoimmunity. - Source: PubMed
Publication date: 2025/09/30
Wu XunWang ZiyiCroce Katherine RLi FangCui JianD'Agati Vivette DSoni Rajesh KTabas IraYamamoto AiZhang Hanrui