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The caveolae‐associated coiled‐coil protein, NECC 2, regulates insulin signalling in Adipocytes
Author(s) -
Trávez Andrés,
RabanalRuiz Yoana,
LópezAlcalá Jaime,
MoleroMurillo Laura,
DíazRuiz Alberto,
GuzmánRuiz Rocío,
Catalán Victoria,
Rodríguez Amaia,
Frühbeck Gema,
Tinahones Francisco J.,
Gasman Stéphane,
Vitale Nicolas,
JiménezGómez Yolanda,
Malagón María M.
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13840
Subject(s) - caveolae , insulin resistance , medicine , insulin receptor , biology , endocrinology , adipocyte , microbiology and biotechnology , caveolin 1 , caveolin , protein kinase b , insulin , phosphorylation , signal transduction , adipose tissue
Adipocyte dysfunction in obesity is commonly associated with impaired insulin signalling in adipocytes and insulin resistance. Insulin signalling has been associated with caveolae, which are coated by large complexes of caveolin and cavin proteins, along with proteins with membrane‐binding and remodelling properties. Here, we analysed the regulation and function of a component of caveolae involved in growth factor signalling in neuroendocrine cells, neuroendocrine long coiled‐coil protein‐2 ( NECC 2), in adipocytes. Studies in 3T3‐L1 cells showed that NECC 2 expression increased during adipogenesis. Furthermore, NECC 2 co‐immunoprecipitated with caveolin‐1 ( CAV 1) and exhibited a distribution pattern similar to that of the components of adipocyte caveolae, CAV 1, Cavin1, the insulin receptor and cortical actin. Interestingly, NECC 2 overexpression enhanced insulin‐activated Akt phosphorylation, whereas NECC 2 downregulation impaired insulin‐induced phosphorylation of Akt and ERK 2. Finally, an up‐regulation of NECC 2 in subcutaneous and omental adipose tissue was found in association with human obesity and insulin resistance. This effect was also observed in 3T3‐L1 adipocytes exposed to hyperglycaemia/hyperinsulinemia. Overall, the present study identifies NECC 2 as a component of adipocyte caveolae that is regulated in response to obesity and associated metabolic complications, and supports the contribution of this protein as a molecular scaffold modulating insulin signal transduction at these membrane microdomains.

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