Quantitative and Statistical Study of the Dynamics of Clathrin-Dependent and -Independent Endocytosis Reveal a Differential Role of EndophilinA2

Bertot, Laëtitia; Grassart, Alexandre; Lagache, Thibault; Nardi, Giacomo; Basquin, Cyril; Olivo‐Marin, Jean‐Christophe; Sauvonnet, Nathalie

doi:10.1016/j.celrep.2018.01.039

Cited by 25 publications

(19 citation statements)

References 35 publications

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“…Therefore, it seems to be more likely that cell surface expression of the IL-2R is regulated by the intracellular levels of iron. Interestingly, the IL-2R is endocytosed via a recently identified endophilin-dependent pathway and not via clathrin-mediated endocytosis (41). It is, thus, tempting to speculate that the endothelin pathway may be dysregulated in the Fe-def cells leading to reduced surface expression of IL-2R but not of other cytokine receptors, which do not use this endocytic route (42).…”

Section: Discussionmentioning

confidence: 99%

Iron Deprivation in Human T Cells Induces Nonproliferating Accessory Helper Cells

et al. 2020

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Iron uptake via the transferrin receptor (CD71) is a pivotal mechanism for T cell proliferation. Yet, it is incompletely understood if targeting of CD71 also affects the differentiation and functional polarization of primary human T cells. In this study, we demonstrate that inhibition of iron ingestion with blocking mAbs against CD71 induces nonproliferating T cells, which release high amounts of IL-2. Targeting of CD71 with blocking or nonblocking mAbs did not alter major signaling pathways and the activation of the transcription factors NF-kB, NFAT, or AP-1 as analyzed in Jurkat T cells. Growth arrest in iron-deficient (Fe-def) T cells was prevented upon addition of exogenous iron in the form of ferric ammonium citrate but was not reversible by exogenous IL-2. Surprisingly, protein synthesis was found to be intact in Fe-def T cells as demonstrated by comparable levels of CD69 upregulation and cytokine production with iron-sufficient T cells upon stimulation with CD3 plus CD28 mAbs. Indeed, high amounts of IL-2 were detectable in the supernatant of Fe-def T cells, which was accompanied with a reduced cell surface expression of IL-2R. When we used such Fedef T cells in allogeneic MLRs, we observed that these cells acquired an accessory cell function and stimulated the proliferation of bystander T cells by providing IL-2. Thus, the results of our study demonstrate that iron deprivation causes nonproliferating, altruistic T cells that can help and stimulate other immune cells by providing cytokines such as IL-2. ImmunoHorizons, 2020, 4: 165-177.

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Section: Discussionmentioning

confidence: 99%

Iron Deprivation in Human T Cells Induces Nonproliferating Accessory Helper Cells

et al. 2020

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“…Hep2 cells (HeLa derivative) and its derivatives expressing the β-chain of IL-2R, Hep2β, were grown in DMEM (1 g/L) (Gibco) supplemented with 10% heat-inactivated FCS (HI-FCS) (Eurobio) at 5% CO 2 at 37°C (44), in the presence of 1 mg/mL G418 (Sigma) for Hep2β cells. CRISPR-Cas9 genome edited Hep2β Dnm2-GFP and Hep2β CLC-GFP cells (25), and the RUSH stable HeLa cell line expressing the ER molecular hook streptavidin-KDEL and the cargo SBP-EGFP-TNFα (45) were described previously. Hep2 and HeLa cells are nonpolarized cells and were always cultured to 70% confluence before infection experiments.…”

Section: Methodsmentioning

confidence: 99%

Shigella promotes major alteration of gut epithelial physiology and tissue invasion by shutting off host intracellular transport

Ferrari

Malardé

Grassart

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Intracellular trafficking pathways in eukaryotic cells are essential to maintain organelle identity and structure, and to regulate cell communication with its environment. Shigella flexneri invades and subverts the human colonic epithelium by the injection of virulence factors through a type 3 secretion system (T3SS). In this work, we report the multiple effects of two S. flexneri effectors, IpaJ and VirA, which target small GTPases of the Arf and Rab families, consequently inhibiting several intracellular trafficking pathways. IpaJ and VirA induce large-scale impairment of host protein secretion and block the recycling of surface receptors. Moreover, these two effectors decrease clathrin-dependent and -independent endocytosis. Therefore, S. flexneri infection induces a global blockage of host cell intracellular transport, affecting the exchange between cells and their external environment. The combined action of these effectors disorganizes the epithelial cell polarity, disturbs epithelial barrier integrity, promotes multiple invasion events, and enhances the pathogen capacity to penetrate into the colonic tissue in vivo.

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“…However, although IL-2 was reported to be internalized by FEME in T cells (Boucrot et al 2015), it has been suggested that the characteristics found for uptake of IL-2 receptor subunits after crosslinking with antibodies are affected by the antibodies, and that the receptor subunits in spite of many similarities are endocytosed by a different mechanism than FEME (Ferreira and Boucrot 2018). A recent publication reports that endophilin A2 is required for dynamin recruitment during endocytosis of the IL-2 receptor (Bertot et al 2018). In contrast, dynamin was still recruited to clathrin-coated pits after knockdown of endophilin A2, and importantly, in the control situation endophilin was recruited to all clathrin-coated pits, not only to a subpopulation, meaning that endophilin cannot be used as a marker for clathrin-independent endocytosis.…”

Section: Introductionmentioning

confidence: 99%

Clathrin-independent endocytosis: an increasing degree of complexity

Sandvig

Kavaliauskiene

Skotland

2018

Histochem Cell Biol

157

177

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This article aims at providing an update on the complexity of clathrin-independent endocytosis. It is now almost 30 years since we first wrote a review about its existence; at that time many people believed that with the exception of macropinocytosis, which will only be briefly mentioned in this review, all uptake could be accounted for by clathrin-dependent endocytosis. Now it is generally accepted that there are different clathrin-independent mechanisms, some of them regulated by ligands and membrane lipid composition. They can be both dynamin-dependent and -independent, meaning that the uptake cannot be accounted for by caveolae and other dynamin-dependent processes such as tubular structures that can be induced by toxins, e.g. Shiga toxin, or the fast endophilin mediated endocytosis recently described. Caveolae seem to be mostly quite stable structures with other functions than endocytosis, but evidence suggests that they may have cell-type dependent functions. Although several groups have been working on endocytic mechanisms for years, and new advanced methods have improved our ability to study mechanistic details, there are still a number of important questions we need to address, such as: How many endocytic mechanisms does a cell have? How quantitatively important are they? What about the complexity in polarized cells where clathrin-independent endocytosis is differentially regulated on the apical and basolateral poles? These questions are not easy to answer since one and the same molecule may contribute to more than one process, and manipulating one mechanism can affect another. Also, several inhibitors of endocytic processes commonly used turn out to be less specific than originally thought. We will here describe the current view of clathrin-independent endocytic processes and the challenges in studying them.

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Quantitative and Statistical Study of the Dynamics of Clathrin-Dependent and -Independent Endocytosis Reveal a Differential Role of EndophilinA2

Cited by 25 publications

References 35 publications

Iron Deprivation in Human T Cells Induces Nonproliferating Accessory Helper Cells

Iron Deprivation in Human T Cells Induces Nonproliferating Accessory Helper Cells

Shigella promotes major alteration of gut epithelial physiology and tissue invasion by shutting off host intracellular transport

Clathrin-independent endocytosis: an increasing degree of complexity

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