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  1. Article ; Online: Fast Ultrasound Scanning is a Rapid, Sensitive, Precise and Cost-Effective Method to Monitor Tumor Grafts in Mice.

    Molière, Sébastien / Martinet, Arthur / Jaulin, Amélie / Lodi, Massimo / Chamaraux-Tran, Thien-Nga / Alpy, Fabien / Bierry, Guillaume / Tomasetto, Catherine

    Journal of mammary gland biology and neoplasia

    2024  Volume 29, Issue 1, Page(s) 2

    Abstract: In preclinical studies, accurate monitoring of tumor dynamics is crucial for understanding cancer biology and evaluating therapeutic interventions. Traditional methods like caliper measurements and bioluminescence imaging (BLI) have limitations, ... ...

    Abstract In preclinical studies, accurate monitoring of tumor dynamics is crucial for understanding cancer biology and evaluating therapeutic interventions. Traditional methods like caliper measurements and bioluminescence imaging (BLI) have limitations, prompting the need for improved imaging techniques. This study introduces a fast-scan high-frequency ultrasound (HFUS) protocol for the longitudinal assessment of syngeneic breast tumor grafts in mice, comparing its performance with caliper, BLI measurements and with histological analysis. The E0771 mammary gland tumor cell line, engineered to express luciferase, was orthotopically grafted into immunocompetent C57BL/6 mice. Tumor growth was monitored longitudinally at multiple timepoints using caliper measurement, HFUS, and BLI, with the latter two modalities assessed against histopathological standards post-euthanasia. The HFUS protocol was designed for rapid, anesthesia-free scanning, focusing on volume estimation, echogenicity, and necrosis visualization. All mice developed tumors, only 20.6% were palpable at day 4. HFUS detected tumors as small as 2.2 mm in average diameter from day 4 post-implantation, with an average scanning duration of 47 s per mouse. It provided a more accurate volume assessment than caliper, with a lower average bias relative to reference tumor volume. HFUS also revealed tumor necrosis, correlating strongly with BLI in terms of tumor volume and cellularity. Notable discrepancies between HFUS and BLI growth rates were attributed to immune cell infiltration. The fast HFUS protocol enables precise and efficient tumor assessment in preclinical studies, offering significant advantages over traditional methods in terms of speed, accuracy, and animal welfare, aligning with the 3R principle in animal research.
    MeSH term(s) Animals ; Mice ; Mice, Inbred C57BL ; Cost-Benefit Analysis ; Ultrasonography ; Cell Line, Tumor ; Mammary Neoplasms, Animal ; Necrosis
    Language English
    Publishing date 2024-01-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1327345-0
    ISSN 1573-7039 ; 1083-3021
    ISSN (online) 1573-7039
    ISSN 1083-3021
    DOI 10.1007/s10911-024-09555-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A genetic screen to uncover mechanisms underlying lipid transfer protein function at membrane contact sites.

    Mishra, Shirish / Manohar, Vaishnavi / Chandel, Shabnam / Manoj, Tejaswini / Bhattacharya, Subhodeep / Hegde, Nidhi / Nath, Vaisaly R / Krishnan, Harini / Wendling, Corinne / Di Mattia, Thomas / Martinet, Arthur / Chimata, Prasanth / Alpy, Fabien / Raghu, Padinjat

    Life science alliance

    2024  Volume 7, Issue 6

    Abstract: Lipid transfer proteins mediate the transfer of lipids between organelle membranes, and the loss of function of these proteins has been linked to neurodegeneration. However, the mechanism by which loss of lipid transfer activity leads to ... ...

    Abstract Lipid transfer proteins mediate the transfer of lipids between organelle membranes, and the loss of function of these proteins has been linked to neurodegeneration. However, the mechanism by which loss of lipid transfer activity leads to neurodegeneration is not understood. In
    MeSH term(s) Animals ; Humans ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Retinal Degeneration/genetics ; Drosophila/genetics ; Drosophila/metabolism ; Phospholipid Transfer Proteins/genetics ; Lipids ; Carrier Proteins
    Chemical Substances lipid transfer protein ; Drosophila Proteins ; Phospholipid Transfer Proteins ; Lipids ; Carrier Proteins
    Language English
    Publishing date 2024-03-18
    Publishing country United States
    Document type Journal Article
    ISSN 2575-1077
    ISSN (online) 2575-1077
    DOI 10.26508/lsa.202302525
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: MOSPD2 is an endoplasmic reticulum-lipid droplet tether functioning in LD homeostasis.

    Zouiouich, Mehdi / Di Mattia, Thomas / Martinet, Arthur / Eichler, Julie / Wendling, Corinne / Tomishige, Nario / Grandgirard, Erwan / Fuggetta, Nicolas / Fromental-Ramain, Catherine / Mizzon, Giulia / Dumesnil, Calvin / Carpentier, Maxime / Reina-San-Martin, Bernardo / Mathelin, Carole / Schwab, Yannick / Thiam, Abdou Rachid / Kobayashi, Toshihide / Drin, Guillaume / Tomasetto, Catherine /
    Alpy, Fabien

    The Journal of cell biology

    2022  Volume 221, Issue 6

    Abstract: Membrane contact sites between organelles are organized by protein bridges. Among the components of these contacts, the VAP family comprises ER-anchored proteins, such as MOSPD2, that function as major ER-organelle tethers. MOSPD2 distinguishes itself ... ...

    Abstract Membrane contact sites between organelles are organized by protein bridges. Among the components of these contacts, the VAP family comprises ER-anchored proteins, such as MOSPD2, that function as major ER-organelle tethers. MOSPD2 distinguishes itself from the other members of the VAP family by the presence of a CRAL-TRIO domain. In this study, we show that MOSPD2 forms ER-lipid droplet (LD) contacts, thanks to its CRAL-TRIO domain. MOSPD2 ensures the attachment of the ER to LDs through a direct protein-membrane interaction. The attachment mechanism involves an amphipathic helix that has an affinity for lipid packing defects present at the surface of LDs. Remarkably, the absence of MOSPD2 markedly disturbs the assembly of lipid droplets. These data show that MOSPD2, in addition to being a general ER receptor for inter-organelle contacts, possesses an additional tethering activity and is specifically implicated in the biology of LDs via its CRAL-TRIO domain.
    MeSH term(s) Endoplasmic Reticulum/metabolism ; Homeostasis ; Lipid Droplets/metabolism ; Membrane Proteins/metabolism ; Mitochondrial Membranes ; Receptors, Chemokine/metabolism
    Chemical Substances Membrane Proteins ; Receptors, Chemokine
    Language English
    Publishing date 2022-04-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.202110044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: FFAT motif phosphorylation controls formation and lipid transfer function of inter-organelle contacts.

    Di Mattia, Thomas / Martinet, Arthur / Ikhlef, Souade / McEwen, Alastair G / Nominé, Yves / Wendling, Corinne / Poussin-Courmontagne, Pierre / Voilquin, Laetitia / Eberling, Pascal / Ruffenach, Frank / Cavarelli, Jean / Slee, John / Levine, Timothy P / Drin, Guillaume / Tomasetto, Catherine / Alpy, Fabien

    The EMBO journal

    2020  Volume 39, Issue 23, Page(s) e104369

    Abstract: Organelles are physically connected in membrane contact sites. The endoplasmic reticulum possesses three major receptors, VAP-A, VAP-B, and MOSPD2, which interact with proteins at the surface of other organelles to build contacts. VAP-A, VAP-B, and ... ...

    Abstract Organelles are physically connected in membrane contact sites. The endoplasmic reticulum possesses three major receptors, VAP-A, VAP-B, and MOSPD2, which interact with proteins at the surface of other organelles to build contacts. VAP-A, VAP-B, and MOSPD2 contain an MSP domain, which binds a motif named FFAT (two phenylalanines in an acidic tract). In this study, we identified a non-conventional FFAT motif where a conserved acidic residue is replaced by a serine/threonine. We show that phosphorylation of this serine/threonine is critical for non-conventional FFAT motifs (named Phospho-FFAT) to be recognized by the MSP domain. Moreover, structural analyses of the MSP domain alone or in complex with conventional and Phospho-FFAT peptides revealed new mechanisms of interaction. Based on these new insights, we produced a novel prediction algorithm, which expands the repertoire of candidate proteins with a Phospho-FFAT that are able to create membrane contact sites. Using a prototypical tethering complex made by STARD3 and VAP, we showed that phosphorylation is instrumental for the formation of ER-endosome contacts, and their sterol transfer function. This study reveals that phosphorylation acts as a general switch for inter-organelle contacts.
    MeSH term(s) Amino Acid Motifs ; Binding Sites ; Endoplasmic Reticulum/metabolism ; Endosomes/metabolism ; Humans ; Lipid Metabolism ; Lipids ; Membrane Proteins/chemistry ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Models, Molecular ; Phosphorylation ; Protein Binding ; Receptors, Chemokine/chemistry ; Receptors, Chemokine/genetics ; Receptors, Chemokine/metabolism ; Vesicular Transport Proteins/chemistry ; Vesicular Transport Proteins/genetics ; Vesicular Transport Proteins/metabolism
    Chemical Substances Lipids ; MOSPD2 protein, human ; Membrane Proteins ; Receptors, Chemokine ; VAPA protein, human ; VAPB protein, human ; Vesicular Transport Proteins
    Language English
    Publishing date 2020-10-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.15252/embj.2019104369
    Database MEDical Literature Analysis and Retrieval System OnLINE

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