Open AccessThe Long Coiled-Coil Protein NECC2 Is Associated to Caveolae and MODULATES NGF/TrkA Signaling IN PC12 CELLS
Author(s) -
Alberto DíazRuiz,
Yoana Rabanal-Ruíz,
Andrés Trávez,
Francisco GraciaNavarro,
David CruzGarcia,
Maïté Montero-Hadjadje,
Youssef Anouar,
Stéphane Gasman,
Nicolas Vitale,
Rafael Vázquez-Martı́nez,
Marı́a M. Malagón
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0073668
Subject(s) - caveolae , microbiology and biotechnology , tropomyosin receptor kinase a , nerve growth factor , caveolin , caveolin 1 , scaffold protein , signal transduction , protein kinase b , biology , phosphorylation , chemistry , receptor , biochemistry
TrkA-mediated NGF signaling in PC12 cells has been shown to be compartimentalized in specialized microdomains of the plasma membrane, the caveolae, which are organized by scaffold proteins including the member of the caveolin family of proteins, caveolin-1. Here, we characterize the intracellular distribution as well as the biochemical and functional properties of the neuroendocrine long coiled-coil protein 2 (NECC2), a novel long coiled-coil protein selectively expressed in neuroendocrine tissues that contains a predicted caveolin-binding domain and displays structural characteristics of a scaffolding factor. NECC2 distributes in caveolae, wherein it colocalizes with the TrkA receptor, and behaves as a caveolae-associated protein in neuroendocrine PC12 cells. In addition, stimulation of PC12 cells with nerve growth factor (NGF) increased the expression and regulated the distribution of NECC2. Interestingly, knockdown as well as overexpression of NECC2 resulted in a reduction of NGF-induced phosphorylation of the TrkA downstream effector extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2) but not of Akt. Altogether, our results identify NECC2 as a novel component of caveolae in PC12 cells and support the contribution of this protein in the maintenance of TrkA-mediated NGF signaling.