7 research outputs found

    GBF1 and Arf1 interact with Miro and regulate mitochondrial positioning within cells

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    Abstract The spatial organization of cells depends on coordination between cytoskeletal systems and intracellular organelles. The Arf1 small G protein and its activator GBF1 are important regulators of Golgi organization, maintaining its morphology and function. Here we show that GBF1 and its substrate Arf1 regulate the spatial organization of mitochondria in a microtubule-dependent manner. Miro is a mitochondrial membrane protein that interacts through adaptors with microtubule motor proteins such as cytoplasmic dynein, the major microtubule minus end directed motor. We demonstrate a physical interaction between GBF1 and Miro, and also between the active GTP-bound form of Arf1 and Miro. Inhibition of GBF1, inhibition of Arf1 activation, or overexpression of Miro, caused a collapse of the mitochondrial network towards the centrosome. The change in mitochondrial morphology upon GBF1 inhibition was due to a two-fold increase in the time engaged in retrograde movement compared to control conditions. Electron tomography revealed that GBF1 inhibition also resulted in larger mitochondria with more complex morphology. Miro silencing or drug inhibition of cytoplasmic dynein activity blocked the GBF1-dependent repositioning of mitochondria. Our results show that blocking GBF1 function promotes dynein- and Miro-dependent retrograde mitochondrial transport along microtubules towards the microtubule-organizing center, where they form an interconnected network

    Fact-checking Multidimensional Statistic Claims in French

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    International audienceTo strengthen public trust and counter disinformation, computational fact-checking, leveraging digital data sources, attracts interest from the journalists and the computer science community. A particular class of interesting data sources comprises statistics, that is, numerical data compiled mostly by governments, administrations, and international organizations. Statistics are often multidimensional datasets, where multiple dimensions characterize one value, and the dimensions may be organized in hierarchies. This paper describes STATCHECK, a statistic fact-checking system jointly developed by the authors, which are either computer science researchers or fact-checking journalists working for a French-language media with a daily audience of more than 15 millions (aud, 2022). The technical novelty of STATCHECK is twofold: (i) we focus on multidimensional, complex-structure statistics, which have received little attention so far, despite their practical importance; and (ii) novel statistical claim extraction modules for French, an area where few resources exist. We validate the efficiency and quality of our system onlarge statistic datasets (hundreds of millions of facts), including the complete INSEE (French)and Eurostat (European Union) datasets, as well as French presidential election debates

    Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia

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    International audienceRemodeling of the extracellular matrix by carcinoma cells during metastatic dissemination requires formation of actin-based protrusions of the plasma membrane called invadopodia, where the trans-membrane type 1 matrix metalloproteinase (MT1-MMP) accumulates. Here, we describe an interaction between the exocyst complex and the endosomal Arp2/3 activator Wiskott-Aldrich syndrome protein and Scar homolog (WASH) on MT1-MMP–containing late endosomes in invasive breast carcinoma cells. We found that WASH and exocyst are required for matrix degradation by an exocytic mechanism that involves tubular connections between MT1-MMP–positive late endosomes and the plasma membrane in contact with the matrix. This ensures focal delivery of MT1-MMP and supports pericellular matrix degradation and tumor cell invasion into different pathologically relevant matrix environments. Our data suggest a general mechanism used by tumor cells to breach the basement membrane and for invasive migration through fibrous collagen-enriched tissues surrounding the tumor
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