Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion

Li, Kai; Jian, Youli; Sun, Xiaojuan; Yang, Chengkui; Gao, Zhiyang; Zhang, Zhili; Liu, Xuezhao; Li, Yang; Xu, Jing; Jing, Yudong; Mitani, Shohei; He, Sudan; Yang, Chonglin

doi:10.1083/jcb.201506081

Cited by 75 publications

(114 citation statements)

References 59 publications

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“…Although WDR81 was earlier suggested being an integral membrane spanning protein (69), both our bioinformatic and biochemical ( Figure 3B) analysis suggest that WDR81 is cytosolic and it associates with EEA1 positive and LAMP1 positive endosomal membranes. This is in agreement with the recent findings of Liu et al (72) who showed the association/colocalization of WDR81 with EEA1-and Rab7-positive endosomes.…”

Section: Discussionsupporting

confidence: 94%

“…Our data suggest that the WDR81-WDR91 complex is required for the trafficking and degradation of internalized PM proteins and facilitates delivery of cargo from early to late endosomal/lysosomal compartments. Our findings are consistent with a recent report from Liu et al (72), published during preparation of our manuscript, which identified the Caenorhabditis elegans orthologues of WDR81 and 91 (respectively F25C9.1 or SORF-2 and ZK563.5 or SORF-1), as genes required for partial rescue of the endosome/lysosome fusion defects present in coelomocytes of C. elegans vps18 mutants and showed that mammalian WDR81 and WDR91 form a complex functioning in endolysosomal trafficking.…”

Section: Discussionsupporting

confidence: 94%

“…Taken together, our results suggest that this is due to a perturbation in delivery of endocytosed cargo to lysosomes caused by accumulation of cargo in early endosomal compartments. The recent findings of Liu et al provide important mechanistic insight into our own observations on the defect of tetherin trafficking and degradation seen in WDR81‐ and WDR91‐depleted cells. They showed that WDR81 and WDR91 were able to regulate phosphatidylinositol 3‐phosphate (PtdIns3P) levels on endosomal membranes.…”

Section: Discussionmentioning

confidence: 62%

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A Genetic Screen Identifies a Critical Role for the WDR81‐WDR91 Complex in the Trafficking and Degradation of Tetherin

Rapiteanu

Davis

Williamson

et al. 2016

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Tetherin (BST2/CD317) is a viral restriction factor that anchors enveloped viruses to host cells and limits viral spread. The HIV‐1 Vpu accessory protein counteracts tetherin by decreasing its cell surface expression and targeting it for ubiquitin‐dependent endolysosomal degradation. Although the Vpu‐mediated downregulation of tetherin has been extensively studied, the molecular details are not completely elucidated. We therefore used a forward genetic screen in human haploid KBM7 cells to identify novel genes required for tetherin trafficking. Our screen identified WDR81 as a novel gene required for tetherin trafficking and degradation in both the presence and absence of Vpu. WDR81 is a BEACH‐domain containing protein that is also required for the degradation of EGF‐stimulated epidermal growth factor receptor (EGFR) and functions in a complex with the WDR91 protein. In the absence of WDR81 the endolysosomal compartment appears swollen, with enlarged early and late endosomes and reduced delivery of endocytosed dextran to cathepsin‐active lysosomes. Our data suggest a role for the WDR81‐WDR91 complex in the fusion of endolysosomal compartments and the absence of WDR81 leads to impaired receptor trafficking and degradation.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 62%

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A Genetic Screen Identifies a Critical Role for the WDR81‐WDR91 Complex in the Trafficking and Degradation of Tetherin

Rapiteanu

Davis

Williamson

et al. 2016

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“…These findings thus reveal a conserved mechanism by which PtdIns3P synthesis is inhibited to allow for the change of lipid identity that accompanies early‐to‐late endosome conversion (Figure ). In addition, these findings provide important insights for understanding the role of WDR81 in cerebellar ataxia, mental retardation and disequilibrium syndrome (CAMRQ2), which is associated with WDR81 mutation …”

Section: Endo‐lysosomal Traffickingmentioning

confidence: 98%

“… While the mechanism governing the Rab5‐to‐Rab7 switch was revealed a few years ago, it remains largely elusive how correct endosomal PtdIns3P levels are achieved to allow for endosome conversion and the change of endosome lipid identity. Recently, C.Y.’s lab identified SORF‐1/WDR91 and SORF‐2/WDR81, 2 novel factors conserved from C elegans to mammals, as essential regulators of PtdIns3P in early‐to‐late endosome conversion . In.…”

Section: Endo‐lysosomal Traffickingmentioning

confidence: 99%

Cell biology in China: Focusing on the lysosome

Yang

Wang

2017

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The view that lysosomes are merely the recycling bins of the cell has changed greatly during recent years. Lysosomes are now known to play a central role in signal transduction, cellular adaptation, plasma membrane repair, immune responses and many other fundamental cellular processes. In conjunction with the seminal discoveries made by international colleagues, many important questions regarding lysosomes are being addressed by Chinese scientists. In this review, we briefly summarize recent exciting findings in China on lysosomal signaling, biogenesis, integrity and physiological functions.

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De Novo Design of A Membrane‐Anchored Probe for Multidimensional Quantification of Endocytic Dynamics

Qiu

Seino

Han

et al. 2022

Adv Healthcare Materials

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As a process of cellular uptake, endocytosis, with gradient acidity in different endocytic vesicles, is vital for the homeostasis of intracellular nutrients and other functions. To study the dynamics of endocytic pathway, a membrane-anchored pH probe, ECGreen, is synthesized to visualize endocytic vesicles under structured illumination microscopy (SIM), a super-resolution technology. Being sensitive to acidity with increasing fluorescence at low pH, ECGreen can differentiate early and late endosomes as well as endolysosomes. Meanwhile, membrane anchoring not only improves the durability of ECGreen, but also provides an excellent anti-photobleaching property for long-time imaging with SIM. Moreover, by taking these advantages of ECGreen, a multidimensional analysis model containing spatial, temporal, and pH information is successfully developed for elucidating the dynamics of endocytic vesicles and their interactions with mitochondria during autophagy, and reveals a fast conversion of endosomes near the plasma membrane.

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Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion

Abstract: C. elegans SORF-1 and SORF-2 and their mammalian homologs WDR91 and WDR81 maintain appropriate PtdIns3P levels in early-to-late endosome conversion by forming a complex with the Beclin1 subunit of the PI3K complex.

Cited by 75 publications

References 59 publications

A Genetic Screen Identifies a Critical Role for the WDR81‐WDR91 Complex in the Trafficking and Degradation of Tetherin

A Genetic Screen Identifies a Critical Role for the WDR81‐WDR91 Complex in the Trafficking and Degradation of Tetherin

Cell biology in China: Focusing on the lysosome

De Novo Design of A Membrane‐Anchored Probe for Multidimensional Quantification of Endocytic Dynamics

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