Trávez, A. (Andrés)

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    The caveolae-associated coiled-coil protein, NECC2, regulates insulin signalling in Adipocytes
    (Wiley, 2018) Gasman, S. (Stéphane); Vitale, N. (Nicolas); Rabanal-Ruiz, Y. (Yoana); Tinahones, F.J. (Francisco J.); Catalan, V. (Victoria); Díaz-Ruiz, A. (Alberto); Guzmán-Ruiz, R. (Rocío); Jiménez-Gómez, Y. (Yolanda); Frühbeck, G. (Gema); Malagon, M.M. (María M.); Molero-Murillo, L. (Laura); López-Alcalá, J. (Jaime); Trávez, A. (Andrés); Rodriguez, A. (Amaia)
    Adipocyte dysfunction in obesity is commonly associated with impaired insulin sig-nalling in adipocytes and insulin resistance. Insulin signalling has been associatedwith caveolae, which are coated by large complexes of caveolin and cavin proteins,along with proteins with membrane‐binding and remodelling properties. Here, weanalysed the regulation and function of a component of caveolae involved in growthfactor signalling in neuroendocrine cells, neuroendocrine long coiled‐coil protein‐2(NECC2), in adipocytes. Studies in 3T3‐L1 cells showed that NECC2 expressionincreased during adipogenesis. Furthermore, NECC2 co‐immunoprecipitated withcaveolin‐1 (CAV1) and exhibited a distribution pattern similar to that of the compo-nents of adipocyte caveolae, CAV1, Cavin1, the insulin receptor and cortical actin.Interestingly, NECC2 overexpression enhanced insulin‐activated Akt phosphoryla-tion, whereas NECC2 downregulation impaired insulin‐induced phosphorylation ofAkt and ERK2. Finally, an up‐regulation ofNECC2in subcutaneous and omental adi-pose tissue was found in association with human obesity and insulin resistance. Thiseffect was also observed in 3T3‐L1 adipocytes exposed to hyperglycaemia/hyperin-sulinemia. Overall, the present study identifies NECC2 as a component of adipocytecaveolae that is regulated in response to obesity and associated metabolic complica-tions, and supports the contribution of this protein as a molecular scaffold modulat-ing insulin signal transduction at these membrane microdomains.