title: The long coiled-coil protein NECC2 is associated to caveolae and modulates NGF/TrkA signaling in PC12 cells [corrected].
abstract: 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.
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain ; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Díaz-Ruiz
authors.forename: Yoana
authors.initials: Y
authors.lastname: Rabanal-Ruiz
authors.forename: Andrés
authors.initials: A
authors.lastname: Trávez
authors.forename: Francisco
authors.initials: F
authors.lastname: Gracia-Navarro
authors.forename: David
authors.initials: D
authors.lastname: Cruz-García
authors.forename: Maité
authors.initials: M
authors.lastname: Montero-Hadjadje
authors.forename: Youssef
authors.initials: Y
authors.lastname: Anouar
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gasman
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vitale
authors.forename: Rafael
authors.initials: R
authors.lastname: Vázquez-Martínez
authors.forename: María M
authors.initials: MM
authors.lastname: Malagón
mesh_terms: D000818:Animals; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051242:Caveolin 1; C000589187:Jakmip3 protein, rat; D008565:Membrane Proteins; D049452:Green Fluorescent Proteins; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
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