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22 septembre 2017: 1 événement

  • Département Biologie Cellulaire

    Vendredi 22 septembre 2017 11:00-12:30 - Vesa Markus OLKKONEN - Minerva Foundation Institute for Medical Research, Helsingfors, Finlande, invité par Francesca Giordano

    OSBP-related protein 2 (ORP2) : A new regulatory node between cellular energy metabolism, adhesion, migration and proliferation

    Résumé : ORP2 is a ubiquitously expressed OSBP-related protein previously implicated in triacylglycerol (TG) metabolism at endoplasmic reticulum (ER) - lipid droplet (LD) contacts, cholesterol transport, and adrenocortical steroidogenesis. We now characterize the functional role of ORP2 by employing ORP2-knock-out (KO) hepatoma cells generated by CRISPR-Cas9 gene editing. Loss of ORP2 did not affect the major cellular phospholipids, cholesterol, or oxysterols, nor the quantity of ER-LD contact sites. However, the knock-out resulted in reduced expression of SREBP-1 target genes and mRNAs encoding glycolytic enzymes, defective TG synthesis and storage, inhibition of LD growth upon fatty acid loading, reduction of glucose uptake, glycogen synthesis, glycolysis (ECAR) and Akt activity. ORP2 was found to form a physical complex with key controllers of Akt, Cdc37 and Hsp90. In addition to the metabolic phenotypes, the ORP2-KO cells showed defects in adhesion, lamellipodieae formation, migration and proliferation, and the ORP2 interactome contained, in addition to Cdc37, a number of actin regulatory components. The putative lipid transport steps that ORP2 function may involve are as yet unknown, albeit we find a sterol-PI4P countertransport function quite possible.
    To conclude, the present study identifies ORP2 as new regulatory node between cellular energy metabolism, adhesion, migration and proliferation.

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    En savoir plus : Département Biologie Cellulaire