Single Particle Tracking Reveals that EGFR Signaling Activity Is Amplified in Clathrin-Coated Pits

Ibach, Jenny; Radon, Yvonne; Gelléri, Márton; Sonntag, MH Michael; Brunsveld, Luc; Bastiaens, Philippe I. H.; Verveer, Peter J.

doi:10.1371/journal.pone.0143162

Cited by 66 publications

(68 citation statements)

References 57 publications

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“…In a few other NMJ chains, a two-, four-state or five-state models provided the best fit. The apparent diffusion coefficients of the additional states in the four- or five-state models were similar to that of either the slow mobile or fast mobile diffusive states, suggesting degenerate diffusive states as previously observed70. We therefore analysed the parameters of the three-state model in Fig.…”

Section: Methodssupporting

confidence: 63%

In vivo single-molecule imaging of syntaxin1A reveals polyphosphoinositide- and activity-dependent trapping in presynaptic nanoclusters

et al. 2016

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Syntaxin1A is organized in nanoclusters that are critical for the docking and priming of secretory vesicles from neurosecretory cells. Whether and how these nanoclusters are affected by neurotransmitter release in nerve terminals from a living organism is unknown. Here we imaged photoconvertible syntaxin1A-mEos2 in the motor nerve terminal of Drosophila larvae by single-particle tracking photoactivation localization microscopy. Opto- and thermo-genetic neuronal stimulation increased syntaxin1A-mEos2 mobility, and reduced the size and molecular density of nanoclusters, suggesting an activity-dependent release of syntaxin1A from the confinement of nanoclusters. Syntaxin1A mobility was increased by mutating its polyphosphoinositide-binding site or preventing SNARE complex assembly via co-expression of tetanus toxin light chain. In contrast, syntaxin1A mobility was reduced by preventing SNARE complex disassembly. Our data demonstrate that polyphosphoinositide favours syntaxin1A trapping, and show that SNARE complex disassembly leads to syntaxin1A dissociation from nanoclusters. Lateral diffusion and trapping of syntaxin1A in nanoclusters therefore dynamically regulate neurotransmitter release.

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Section: Methodssupporting

confidence: 63%

In vivo single-molecule imaging of syntaxin1A reveals polyphosphoinositide- and activity-dependent trapping in presynaptic nanoclusters

et al. 2016

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“…CME controls EGFR signaling through various mechanisms. At the PM, clustering of EGFR in clathrin-coated pits (CCPs) is required to optimize receptor phosphorylation, and to amplify and spatially constrain EGFR signaling (Garay et al, 2015;Ibach et al, 2015). AP2 exerts a critical function during the assembly of CCPs and it is essential to maintain the right vesicle size, with predictable consequences for receptor clustering and signaling (Aguet et al, 2013;Kadlecova et al, 2017;Miller et al, 2015).…”

Section: Temporal Regulation Of Egfr Signaling By Endocytosismentioning

confidence: 99%

Emerging functions of the EGFR in cancer

2017

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The physiological function of the epidermal growth factor receptor (EGFR) is to regulate epithelial tissue development and homeostasis. In pathological settings, mostly in lung and breast cancer and in glioblastoma, the EGFR is a driver of tumorigenesis. Inappropriate activation of the EGFR in cancer mainly results from amplification and point mutations at the genomic locus, but transcriptional upregulation or ligand overproduction due to autocrine/paracrine mechanisms has also been described. Moreover, the EGFR is increasingly recognized as a biomarker of resistance in tumors, as its amplification or secondary mutations have been found to arise under drug pressure. This evidence, in addition to the prominent function that this receptor plays in normal epithelia, has prompted intense investigations into the role of the EGFR both at physiological and at pathological level. Despite the large body of knowledge obtained over the last two decades, previously unrecognized (herein defined as ‘noncanonical’) functions of the EGFR are currently emerging. Here, we will initially review the canonical ligand‐induced EGFR signaling pathway, with particular emphasis to its regulation by endocytosis and subversion in human tumors. We will then focus on the most recent advances in uncovering noncanonical EGFR functions in stress‐induced trafficking, autophagy, and energy metabolism, with a perspective on future therapeutic applications.

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“…Several proteins and lipids have been shown to reside in, and others to be excluded from, domains displaying distinct membrane order. Confocal, single-particle, FLIM-FRET, and FCS measurements have documented the confinement of specific effectors in distinct plasma membrane domains [142, 160, 226–229]. Moreover, membrane order has been implicated in the modulation of spatially localized signaling events.…”

Section: Dysregulation Of Plasma Membrane Biochemical and Biophysicalmentioning

confidence: 99%

Functional link between plasma membrane spatiotemporal dynamics, cancer biology, and dietary membrane-altering agents

Erazo-Oliveras

Fuentes

Wright

et al. 2018

Cancer Metastasis Rev

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The cell plasma membrane serves as a nexus integrating extra- and intracellular components, which together enable many of the fundamental cellular signaling processes that sustain life. In order to perform this key function, plasma membrane components assemble into well-defined domains exhibiting distinct biochemical and biophysical properties that modulate various signaling events. Dysregulation of these highly dynamic membrane domains can promote oncogenic signaling. Recently, it has been demonstrated that select membrane-targeted dietary bioactives (MTDBs) have the ability to remodel plasma membrane domains and subsequently reduce cancer risk. In this review, we focus on the importance of plasma membrane domain structural and signaling functionalities as well as how loss of membrane homeostasis can drive aberrant signaling. Additionally, we discuss the intricacies associated with the investigation of these membrane domain features and their associations with cancer biology. Lastly, we describe the current literature focusing on MTDBs, including mechanisms of chemoprevention and therapeutics in order to establish a functional link between these membrane-altering biomolecules, tuning of plasma membrane hierarchal organization, and their implications in cancer prevention.

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Single Particle Tracking Reveals that EGFR Signaling Activity Is Amplified in Clathrin-Coated Pits

Cited by 66 publications

References 57 publications

In vivo single-molecule imaging of syntaxin1A reveals polyphosphoinositide- and activity-dependent trapping in presynaptic nanoclusters

In vivo single-molecule imaging of syntaxin1A reveals polyphosphoinositide- and activity-dependent trapping in presynaptic nanoclusters

Emerging functions of the EGFR in cancer

Functional link between plasma membrane spatiotemporal dynamics, cancer biology, and dietary membrane-altering agents

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