The endocytic matrix

Scita, Giorgio; Fiore, Pier Paolo Di

doi:10.1038/nature08910

Cited by 415 publications

(425 citation statements)

References 81 publications

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“…It is well established that signal transduction pathways that are downstream of tyrosine kinase receptors are modulated not only by the identities of protein-protein interactions but also by the colocalization of signal transducers in membrane domains or, more broadly, in organelles and vesicles 78 . This notion has been recently applied to MET: the prevailing view that the activated receptor recruits signalling effectors at the plasma membrane, which in turn stimulate diffusible intermediates in the cytosol, has now been expanded by the finding that MET signals can also emanate from endosomal compartments.…”

Section: Regulation Of Met Signallingmentioning

confidence: 99%

MET signalling: principles and functions in development, organ regeneration and cancer

Trusolino

Bertotti

Comoglio

2010

Nat Rev Mol Cell Biol

1,059

1,076

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The MET tyrosine kinase receptor (also known as the HGF receptor) promotes tissue remodelling, which underlies developmental morphogenesis, wound repair, organ homeostasis and cancer metastasis, by integrating growth, survival and migration cues in response to environmental stimuli or cell-autonomous perturbations. The versatility of MET-mediated biological responses is sustained by qualitative and quantitative signal modulation. Qualitative mechanisms include the engagement of dedicated signal transducers and the subcellular compartmentalization of MET signalling pathways, whereas quantitative regulation involves MET partnering with adaptor amplifiers or being degraded through the shedding of its extracellular domain or through intracellular ubiquitylation. Controlled activation of MET signalling can be exploited in regenerative medicine, whereas MET inhibition might slow down tumour progression.Throughout embryogenesis, cells bud off from developing tissues and move outwards to shape and pattern the complex architecture of prospective organs 1 . A similar process occurs in adult life during wound healing and tissue repair, when lingering cells migrate into injury sites to recreate the pre-existing structures 2 . The acquisition of cell motility is necessary, but not sufficient, for this event. Cells that detach from their neighbours must elude anoikis, a form of apoptotic cell death that occurs when cells lose adhesion with the extracellular matrix 3 . Moreover, migratory cells undergo extensive mitotic divisions to produce 'founder populations', which settle in newly forming organs during development or colonize worn tissues during repair 4,5 . The normal phases of embryogenesis and organ regeneration strongly resemble the pathological process of tumour invasiveness: similarly to cells at the wound edge, cells at the tumour's leading front disrupt intercellular contacts and infiltrate the adjacent surroundings, where they resist anoikis and grow before lodging in the blood vessels for systemic dissemination 6 . This resemblance is not simply a biological correlate, it has a common mechanistic basis: cancer cells resurrect the latent schemes of cellular reorganization, which are usually confined to embryonic development and damaged adult organs, and leverage them to become competent for metastasization 7 . The activities -motility, survival and proliferation -that occur in developing, injured and neoplastic tissues embody a biological programme that is defined as 'invasive growth' 8 . This is triggered by extracellular stimuli that regulate the activity of several transcription factors that, in turn, modulate the expression of a number of proteins, ranging from cytoskeletal and cell-cell junctional components to cell cycle regulators and anti-apoptotic effectors 9, 10 . One major environmental inducer of invasive growth is hepatocyte growth factor (HGF, also known as scatter factor), the ligand for the MET tyrosine kinase receptor (also known as the HGF receptor) 11,12,13,14,15,16,17,18,19,20 (Box 1). ...

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Section: Regulation Of Met Signallingmentioning

confidence: 99%

MET signalling: principles and functions in development, organ regeneration and cancer

Trusolino

Bertotti

Comoglio

2010

Nat Rev Mol Cell Biol

1,059

1,076

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“…Epigenomics encompasses chemical modifications of DNA such as methylation, histones, chromatin-remodeling protein complexes [61], and other nuclear proteins, chaperones and some aspects of the dynamic cytoplasmic cytoskeleton [62]. All of these are deeply interlinked with the endocytic matrix [63] that integrates the Senome with the epigenome and genome [63]. …”

Section: Senome Of Cellular Lifementioning

confidence: 99%

“…Electric stimulations are used for the treatment of depression, bipolar mood disorders and mood elevation [147,148]. For the molecular composition of signal transduction and information-processing networks of the Senome , see references 56, 63, 116, 117, 126–137.…”

Section: Introductionmentioning

confidence: 99%

Senomic view of the cell: SenomeversusGenome

Baluška

Miller

2018

Communicative & Integrative Biology

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In the legacy of Thomas Henry Huxley, and his ‘epigenetic’ philosophy of biology, cells are proposed to represent a trinity of three memory-storing media: Senome, Epigenome, and Genome that together comprise a cell-wide informational architecture. Our current preferential focus on the Genome needs to be complemented by a similar focus on the Epigenome and a here proposed Senome, representing the sum of all the sensory experiences of the cognitive cell and its sensing apparatus. Only then will biology be in a position to embrace the whole complexity of the eukaryotic cell, understanding its true nature which allows the communicative assembly of cells in the form of sentient multicellular organisms.

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“…2 As a consequence, cell surface receptors such as the epidermal growth factor receptor (EGFR) are increasingly being regarded as important regulators of downstream signalling. 1,3 The number of EGFR molecules at the cell surface is regulated by a number of dynamical processes ( Fig. 1A): newly produced receptors are translocated to the cell membrane, while receptors at the cell surface are constantly exchanged with intracellular endosomal compartments via clathrin-mediated endocytosis.…”

Section: Introductionmentioning

confidence: 99%

The EGFR demonstrates linear signal transmission

et al. 2014

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Cells sense information encoded in extracellular ligand concentrations and process it using intracellular signalling cascades. Using mathematical modelling and high-throughput imaging of individual cells, we studied how a transient extracellular growth factor signal is sensed by the epidermal growth factor receptor system, processed by downstream signalling, and transmitted to the nucleus. We found that transient epidermal growth factor signals are linearly translated into an activated epidermal growth factor receptor integrated over time. This allows us to generate a simplified model of receptor signaling where the receptor acts as a perfect sensor of extracellular information, while the nonlinear input-output relationship of EGF-EGFR triggered signalling is a consequence of the downstream MAPK cascade alone. Insight, innovation, integrationWe derived an analytical formula from nonlinear models of receptor signalling that have been used to model the signalling of the epidermal growth factor receptor (EGFR). The formula predicted that the cumulative EGFR signalling is linearly dependent on the ligand concentration outside the cell. Quantitative imaging of HeLa cells suggests that the cumulative EGFR signalling indeed depends linearly on the EGF concentration. Our mathematical approach therefore allows a simplified view on complex networks of receptor dynamics and describes the EGFR as a linear sensor of extracellular information encoded in ligand concentrations.

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The endocytic matrix

Cited by 415 publications

References 81 publications

MET signalling: principles and functions in development, organ regeneration and cancer

MET signalling: principles and functions in development, organ regeneration and cancer

Senomic view of the cell: SenomeversusGenome

The EGFR demonstrates linear signal transmission

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