Localized Intercellular Transfer of Ephrin-As by Trans-endocytosis Enables Long-Term Signaling

Valenzuela, Juan Pablo; Perez, Franck

doi:10.1016/j.devcel.2019.11.013

Cited by 18 publications

(20 citation statements)

References 71 publications

(112 reference statements)

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“…Interestingly, we also observed shuttling of smaller EphB6:ephrinB1 clusters towards the ephrinB1-expressing cells along the membrane protrusions (Figure 1C and Video 1). These data confirm ephrinB1 as a cognate ligand of EphB6, and illustrate that EphB6, despite its lack of catalytic activity, retains a capacity for clustering akin to its kinase-active counterparts 31,32 .…”

Section: Ephb6 and Ephrinb1 Co-cluster At The Plasma Membrane In Transsupporting

confidence: 58%

Co-clustering of EphB6 and ephrinB1 in trans suppresses cancer cell invasion

Liang

Geoghegan

Mlodzianoski

et al. 2022

Preprint

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EphB6 is an understudied ephrin receptor tyrosine pseudokinase, the expression of which is downregulated in multiple types of metastatic cancers. Compared to its kinase-active counterparts, how EphB6 regulates signal transduction in the absence of intrinsic kinase activity remains unknown. Here, we unveil the molecular details of key signal transduction mechanisms driven by EphB6. We identify ephrinB1 as a cognate ligand of EphB6 and demonstrate EphB6’s ability to form extensive co-clusters at the plasma membrane upon binding ephrinB1 in trans across cell-cell contacts, which are resistant to endocytosis. Using super resolution microscopy, correlative light and electron microscopy and cryo-electron tomography, we reveal that co clustering of EphB6 and ephrinB1 promotes the formation of unprecedented double membrane tubular structure interconnecting cells. Importantly, phenotypically, co-clustering of EphB6 and ephrinB1 and the resulting tubular structures suppress cancer cell invasion by prolonging cell-cell contacts, rationalising a role for EphB6 pseudokinase as a tumor suppressor when interacting with its ligands in trans.

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Section: Ephb6 and Ephrinb1 Co-cluster At The Plasma Membrane In Transsupporting

confidence: 58%

Co-clustering of EphB6 and ephrinB1 in trans suppresses cancer cell invasion

Liang

Geoghegan

Mlodzianoski

et al. 2022

Preprint

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“…However, trogocytosis is a more general cellular phenomenon that is not limited to immune cells [31]. It has been described in a variety of cellular interactions including microglial presynaptic remodeling [32,33], trogocytosis of oocyte proteins by sperm before fertilization [34], during embryonic development [35][36][37], stromal cell protein trogocytosis by cancer cells [38], erythrocyte interactions with epithelia [39], and parasite interactions with neutrophils to help evade immune detection [40][41][42][43]. It has also been implicated in cell-cell spread of intracellular bacteria such as Francisella tularensis [44] and viral pathogens [10,45,46].…”

Section: Trogocytosismentioning

confidence: 99%

Lymphocytes and Trogocytosis-Mediated Signaling

Reed

Reichelt

Wetzel

2021

Cells

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Trogocytosis is the intercellular transfer of membrane and membrane-associated molecules. This underappreciated process has been described in a variety of biological settings including neuronal remodeling, fertilization, viral and bacterial spread, and cancer, but has been most widely studied in cells of the immune system. Trogocytosis is performed by multiple immune cell types, including basophils, macrophages, dendritic cells, neutrophils, natural killer cells, B cells, γδ T cells, and CD4+ and CD8+ αβ T cells. Although not expressed endogenously, the presence of trogocytosed molecules on cells has the potential to significantly impact an immune response and the biology of the individual trogocytosis-positive cell. Many studies have focused on the ability of the trogocytosis-positive cells to interact with other immune cells and modulate the function of responders. Less understood and arguably equally important is the impact of these molecules on the individual trogocytosis-positive cell. Molecules that have been reported to be trogocytosed by cells include cognate ligands for receptors on the individual cell, such as activating NK cell ligands and MHC:peptide. These trogocytosed molecules have been shown to interact with receptors on the trogocytosis-positive cell and mediate intracellular signaling. In this review, we discuss the impact of this trogocytosis-mediated signaling on the biology of the individual trogocytosis-positive cell by focusing on natural killer cells and CD4+ T lymphocytes.

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“…As episodes of BCR-LEM separation in the embryo last longer than cohesion needs to recover, mechanisms beyond direct cell contact must control detachment. Signaling across a detachment gap could be mediated by filopodia or exosomes (Gong et al, 2016;Takasugi et al, 2017;Valenzuela and Perez, 2020), which would require proximity to the BCR, but not intimate contact.…”

Section: Lem-bcr Interactionsmentioning

confidence: 99%

Capillarity and active cell movement at mesendoderm translocation in the Xenopus gastrula

et al. 2021

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During Xenopus gastrulation, leading edge mesendoderm (LEM) advances animally as wedge-shaped cell mass over the vegetally moving blastocoel roof (BCR). We show that close contact across the BCR-LEM interface correlates with attenuated net advance of the LEM, which is therefore pulled forward by tip cells while the remaining LEM frequently separates from the BCR. Nevertheless, lamellipodia persist on the detached LEM surface. They attach to adjacent LEM cells and depend on PDGF-A, cell surface fibronectin and cadherin. We argue that active cell motility on the LEM surface prevents adverse capillary effects in the liquid LEM tissue as it moves by being pulled. It counters tissue surface tension effects with oriented cell movement and bulges the LEM surface out to keep it close to the curved BCR without attaching to it. Proximity to the BCR is necessary in turn for the maintenance and orientation of lamellipodia that permit mass cell movement with minimal substratum contact. Together with a similar process in epithelial invagination, vertical telescoping, the cell movement at the LEM surface defines a novel type of cell rearrangement, vertical shearing.

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Localized Intercellular Transfer of Ephrin-As by Trans-endocytosis Enables Long-Term Signaling

Abstract: Highlights d Ephrin-A1 trafficking synchronization allows visualization of its transport to filopodia d Signaling occurs at the tips of filopodia d Ephrin-1-EphA2 interaction induces trans-endocytosis of the complex d Trans-endocytosis enables long-term signaling from lysosomes

Cited by 18 publications

References 71 publications

Co-clustering of EphB6 and ephrinB1 in trans suppresses cancer cell invasion

Co-clustering of EphB6 and ephrinB1 in trans suppresses cancer cell invasion

Lymphocytes and Trogocytosis-Mediated Signaling

Capillarity and active cell movement at mesendoderm translocation in the Xenopus gastrula

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