Conf茅rence de Sara Sigismund de l'European Institute of Oncology
En raison des restrictions de voyage des habitants de Lombardie, le s茅minaire de la professeure Sigismund est annul茅. Une date ult茅rieure sera trouv茅e pour sa venue.
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The integration of distinct internalization routes is crucial听to determine the fate of plasma membrane (PM) receptors and听the output of their signalling pathways. Contact sites between听cellular organelles adds a further layer of regulation by听creating microdomains that favour different signalling and听metabolic pathways. These regulatory mechanisms are relevant听to the epidermal growth factor receptor (EGFR). We found that,听while clathrin-mediated endocytosis (CME) is mainly involved听in EGFR recycling and sustaining signalling, EGFR听internalization through non-clathrin endocytosis (NCE) leads听primarily to receptor degradation and signal extinction,听representing a crucial safety mechanism to protect cells from听overstimulation. Internalization via NCE involves the听formation of tripartite contact sites between the PM, the听endoplasmic reticulum (ER) and the mitochondria, where EGF-dependent localized Ca2+ signalling occurs and propagate. Ca2+听release is in turn needed for the fission of NCE vesicular听structures and their release in the cytosol. Thus, NCE, by听targeting EGFRs to degradation, restricts EGFR signalling; it听also exerts a positive role in promoting localized Ca2+听signalling, possibly activating a wider cellular response and听regulating cellular processes that extend beyond those听associated with the canonical EGFR signalling pathway. Through听a combination of mathematical modelling and wet-lab听experiments, we are currently elucidating how the integration听of distinct endocytic pathways and inter-organelle crosstalk听regulate the EGFR physiological responses and which are the听molecular circuitries involved.
EGFR signalling talks to mitochondria through contact sites
By Prof. Sara Sigismund (European Institute of Oncology IRCCS, Milan / AV短视频 of Milan)
2020