Spatial cycles mediated by UNC119 solubilisation maintain Src family kinases plasma membrane localisation

Konitsiotis, Antonios D.; Roßmannek, Lisaweta; Stanoev, Angel; Schmick, Malte; Bastiaens, Philippe I. H.

doi:10.1038/s41467-017-00116-3

Cited by 30 publications

(35 citation statements)

References 67 publications

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“…Since about 30% of the total amount of the Unc119 protein is localized in the outer segment of photoreceptors (Sinha et al , ), excess amounts of Unc119 may abnormally extract and solubilize Tα from the outer segment membrane, leading to mislocalization of Tα to the inner part. Furthermore, a previous study showed that Unc119 overexpression inhibits transport of its cargos, Src family kinases (SFKs), to the target membrane in cultured cells (Konitsiotis et al , ). This study proposes that the Unc119 protein without loading SFKs competitively binds to Arl2/3, which are the small GTPases required for cargo release from Unc119.…”

Section: Discussionmentioning

confidence: 99%

Cul3‐Klhl18 ubiquitin ligase modulates rod transducin translocation during light‐dark adaptation

et al. 2019

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Adaptation is a general feature of sensory systems. In rod photoreceptors, light‐dependent transducin translocation and Ca2+ homeostasis are involved in light/dark adaptation and prevention of cell damage by light. However, the underlying regulatory mechanisms remain unclear. Here, we identify mammalian Cul3‐Klhl18 ubiquitin ligase as a transducin translocation modulator during light/dark adaptation. Under dark conditions, Klhl18−/− mice exhibited decreased rod light responses and subcellular localization of the transducin α‐subunit (Tα), similar to that observed in light‐adapted Klhl18+/+ mice. Cul3‐Klhl18 promoted ubiquitination and degradation of Unc119, a rod Tα‐interacting protein. Unc119 overexpression phenocopied Tα mislocalization observed in Klhl18−/− mice. Klhl18 weakly recognized casein kinase‐2‐phosphorylated Unc119 protein, which is dephosphorylated by Ca2+‐dependent phosphatase calcineurin. Calcineurin inhibition increased Unc119 expression and Tα mislocalization in rods. These results suggest that Cul3‐Klhl18 modulates rod Tα translocation during light/dark adaptation through Unc119 ubiquitination, which is affected by phosphorylation. Notably, inactivation of the Cul3‐Klhl18 ligase and calcineurin inhibitors FK506 and cyclosporine A that are known immunosuppressant drugs repressed light‐induced photoreceptor damage, suggesting potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Cul3‐Klhl18 ubiquitin ligase modulates rod transducin translocation during light‐dark adaptation

et al. 2019

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“…The two homologous proteins UNC119A and UNC119B have been proposed to be involved in cellular shuttling, subcellular localization, and activity of N‐terminally myristoylated proteins including c‐Src . Similarly to other solubilizing factors, the UNC119s sequester the lipid anchors of peripheral membrane proteins in their hydrophobic pockets, thereby facilitating cytosolic diffusion of these proteins .…”

Section: Figurementioning

confidence: 99%

“…Similarly to other solubilizing factors, the UNC119s sequester the lipid anchors of peripheral membrane proteins in their hydrophobic pockets, thereby facilitating cytosolic diffusion of these proteins . Cellular studies have recently shown that the UNC119s are required in order to sustain the PM localization of myristoylated Src protein …”

Section: Figurementioning

confidence: 99%

“…Interfering with UNC119–Src interactions would consequently constitute a possible means to counteract oncogenic Src signaling. However, the underlying mechanism by which the UNC119s regulate the membrane binding of myristoylated proteins remains poorly characterized, because most of these studies have been carried out either in the absence of membranes or in cellulo . To address this issue and to reveal the mechanism of the UNC119–Src membrane interaction, we have explored here the interaction between a myristoylated peptide derived from the N terminus of c‐Src(2–9) (Myr‐Src), containing three Lys residues, and anionic model biomembranes.…”

Section: Figurementioning

confidence: 99%

“…Thanks to the high affinity of UNC119A ( K d =91 n m ) towards Myr‐Src, UNC119A competes with the membrane, thereby impairing fast membrane insertion of Myr‐Src. Recent studies have reported that displacement of myristoylated peptides from UNC119 can be facilitated by Arl2/3 in a GTP‐dependent manner (myristoylated peptides are mainly localized at the recycling endosome). Under these conditions, the decrease in membrane binding affinity of Myr‐Src in the presence of UNC119A is consequently solely due to a drop in k +1.…”

Section: Figurementioning

confidence: 99%

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UNC119A Decreases the Membrane Binding of Myristoylated c‐Src

et al. 2018

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Plasma membrane localization of myristoylated c-Src, a proto-oncogene protein-tyrosine kinase, is required for its signaling activity. Recent studies proposed that UNC119 protein functions as a solubilizing factor for myristoylated proteins, thereby regulating their subcellular distribution and signaling. The underlying molecular mechanism by which UNC119 regulates the membrane binding of c-Src has remained elusive. By combining different biophysical techniques, we have found that binding of a myristoylated c-Src-derived N-terminal peptide (Myr-Src) by UNC119A results in a reduced membrane binding affinity of the peptide, due to the competition of binding to membranes. The dissociation of Myr-Src from membranes is facilitated in the presence of UNC119A, as a consequence of which the clustering propensity of this peptide on the membrane is partially impaired. By these means, UNC119A is able to regulate c-Src spatially in the cytoplasm and on cellular membranes, and this has important implications for its cellular signaling.

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Nano Polymorphism‐Enabled Redox Electrodes for Rechargeable Batteries

Mei

Wang

et al. 2020

Advanced Materials

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dimensions of materials are decreased to the nanoscale, the high surface aspect ratio generates additional engineerable space, which enables the polymorphism of nanomaterials. Recently, nano polymorphism (NPM) has been emerging as a topic of interest in the energy storage field, and research is expected to identify and rationally exploit the "processingstructure-properties" relationships of functional materials of interest in the context of the emerging rechargeable battery applications, particularly for cathode and anode materials. To date, the research on the NPM of rechargeable battery electrodes has achieved significant progress. [1-3] Many electrode materials with various polymorphs, such as traditional layered metal oxides and some emerging types of graphene-like nanosized materials, have been intensively investigated for improving the electrochemical performance of batteries. Moreover, the in-depth underlying storage mechanisms of different polymorphs have been fully or partly revealed using advanced in situ characterization techniques. Based on the previously reported theoretical and experimental results, some potential structural Nano polymorphism (NPM), as an emerging research area in the field of energy storage, and rechargeable batteries, have attracted much attention recently. In this review, the recent progress on the composition and formation of polymorphs, and the evolution processes of different redox electrodes in rechargeable metal-ion, metal-air, and metal-sulfur batteries are highlighted. First, NPM and its significance for rechargeable batteries are discussed. Subsequently, the current NPM modulation strategies of different types of representative electrodes for their corresponding rechargeable battery applications are summarized. The goal is to demonstrate how NPM could tune the intrinsic material properties, and hence, improve their electrochemical activities for each battery type. It is expected that the analysis of polymorphism and electrochemical properties of materials could help identify some "processing-structure-properties" relationships for material design and performance enhancement. Lastly, the current research challenges and potential research directions are discussed to offer guidance and perspectives for future research on NPM engineering.

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Spatial cycles mediated by UNC119 solubilisation maintain Src family kinases plasma membrane localisation

Cited by 30 publications

References 67 publications

Cul3‐Klhl18 ubiquitin ligase modulates rod transducin translocation during light‐dark adaptation

Cul3‐Klhl18 ubiquitin ligase modulates rod transducin translocation during light‐dark adaptation

UNC119A Decreases the Membrane Binding of Myristoylated c‐Src

Nano Polymorphism‐Enabled Redox Electrodes for Rechargeable Batteries

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