ArticleThe Journal of cell biology2015
A conserved polybasic domain mediates plasma membrane targeting of Lgl and its regulation by hypoxia.
Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 77 citations in OpenAlex.
- The cellular stress sensor HSPB1 regulates the membrane localization of amino acid transporter SLC7A5 in breast cancer.The Journal of biological chemistry · 2026Article
- Lgl antagonizes Par complex membrane association to enable neural stem cell asymmetric division.Journal of cell science · 2026Article
- Ubiquitination-Dependent LLGL2 Degradation Drives Colorectal Cancer Progression via THBS3 mRNA Stabilization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Polarity protein Par6 facilitates the processive phosphorylation of Lgl via a dynamic interaction with aPKC.Communications biology · 2025Article
- A PAR6-aPKC-LGL structure reveals how LGL antagonizes aPKC.Nature structural & molecular biology · 2025Article
- PI4P-mediated solid-like Merlin condensates orchestrate Hippo pathway regulation.Science (New York, N.Y.) · 2024Article
- Atypical Protein Kinase C Promotes its own Asymmetric Localisation by Phosphorylating Cdc42 in thebioRxiv : the preprint server for biology · 2024Article
- Recombinant biosensors for multiplex and super-resolution imaging of phosphoinositides.The Journal of cell biology · 2024Article
- Elucidating the Membrane Binding Process of a Disordered Protein: Dynamic Interplay of Anionic Lipids and the Polybasic Region.ACS physical chemistry Au · 2024Article
- PI(4,5)P2: signaling the plasma membrane.The Biochemical journal · 2022Article
- aPKC regulates apical constriction to prevent tissue rupture in the Drosophila follicular epithelium.Current biology : CB · 2022Article
- Apical-basal polarity and the control of epithelial form and function.Nature reviews. Molecular cell biology · 2022Review
- Minimal functional domains of the core polarity regulator Dlg.Biology open · 2022Article
- Hypoxia controls plasma membrane targeting of polarity proteins by dynamic turnover of PI4P and PI(4,5)P2.eLife · 2022Article
- Multi-parametric functional imaging of cell cultures and tissues with a CMOS microelectrode array.Lab on a chip · 2022Article
- Pole position: How plant cells polarize along the axes.The Plant cell · 2022Review
- Membrane Lipids in Epithelial Polarity: Sorting out the PIPs.Frontiers in cell and developmental biology · 2022Review
- Electrostatic plasma membrane targeting contributes to Dlg function in cell polarity and tumorigenesis.Development (Cambridge, England) · 2021Article
- theLiTE™: A Screening Platform to Identify Compounds that Reinforce Tight Junctions.Frontiers in pharmacology · 2021Review
- Scribble, Lgl1, and myosin II form a complex in vivo to promote directed cell migration.Molecular biology of the cell · 2020Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
Abstract
Lethal giant larvae (Lgl) plays essential and conserved functions in regulating both cell polarity and tumorigenesis in Drosophila melanogaster and vertebrates. It is well recognized that plasma membrane (PM) or cell cortex localization is crucial for Lgl function in vivo, but its membrane-targeting mechanisms remain poorly understood. Here, we discovered that hypoxia acutely and reversibly inhibits Lgl PM targeting through a posttranslational mechanism that is independent of the well-characterized atypical protein kinase C (aPKC) or Aurora kinase-mediated phosphorylations. Instead, we identified an evolutionarily conserved polybasic (PB) domain that targets Lgl to the PM via electrostatic binding to membrane phosphatidylinositol phosphates. Such PB domain-mediated PM targeting is inhibited by hypoxia, which reduces inositol phospholipid levels on the PM through adenosine triphosphate depletion. Moreover, Lgl PB domain contains all the identified phosphorylation sites of aPKC and Aurora kinases, providing a molecular mechanism by which phosphorylations neutralize the positive charges on the PB domain to inhibit Lgl PM targeting.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.