Molecular mechanisms involved in CRH receptors signaling

Group Leader

Dr. Susana Silberstein
See CV

Postdocs

Verónica G. Piazza.

PhD Students

Natalia G. Armando, Paula A. dos Santos Claro.

The main goal of our group is to elucidate the molecular mechanisms of corticotrophin- releasing hormone (CRH) signaling in its physiological contexts through the identification of the molecular components involved in the activation of its effectors (cyclic AMP, kinases, calcium).

The molecular pathways that mediate CRH signaling and its related peptides are explored with molecular and pharmacological approaches. To that end, we use as models cell lines that express CRH receptors (CRHR1 and CRHR2), in which proteomic analyses are conducted to generate hypotheses that can be then tested using molecular and cell biology tools.

These results contribute to the knowledge of the mechanisms of action and the identification of new signaling pathways and their involved proteins, which can lead to the discovery of new therapeutic targets for diseases associated with the CRH system.

Publications related to this project

  • dos Santos Claro PA, Inda C, Armando NG, Piazza VG, Attorressi A, Silberstein S.
    Assessing real-time signaling and agonist-induced CRHR1 internalization by optical methods.
    Methods Cell Biol. (In press)
  • Szalai AM 1, Armando NG , Barabas FM , Stefani FD , Giordano L , Bari SE , Cavasotto CN , Silberstein S , Aramendía PF .
    A fluorescence nanoscopy marker for corticotropin-releasing hormone type 1 receptor: computer design, synthesis, signaling effects, super-resolved fluorescence imaging, and in situ affinity constant in cells.
    Phys Chem Chem Phys. 2018. 20(46):29212-29220.
  • Inda C, Bonfiglio JJ, dos Santos Claro PA, Senin SA, Armando NG, Deussing JM, Silberstein S
    cAMP-dependent cell differentiation triggered by activated CRHR1 in hippocampal neuronal cells.
    Sci Rep. 7:1944 (2017)
  • Inda C, Armando NG, dos Santos Claro PA, Silberstein S.
    Endocrinology and the brain: corticotropin-releasing hormone signalling.
    Endocr Connect 6:R99-R120 (2017)
  • Inda C , dos Santos Claro P A, Bonfiglio J J , Senin SA, Maccarrone G, Turck CW, Silberstein S.
    Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling.
    J Cell Biol. 214:181-195 (2016)
  • Bonfiglio, J.J.; Inda, C.; Senin, S.; Maccarrone, G.; Refojo, D.; Giacomini, D.; Turck, C.; Holsboer, F.; Arzt, E.; Silberstein, S.
    B-Raf and CRHR1 internalization mediate biphasic ERK1/2 activation by CRH in hippocampal HT22 cells.
    Molecular Endocrinology 27:491-510 (2013)
  • Bonfiglio J.J., Maccarrone G., Rewerts C, Holsboer F., Arzt E., Turck C., Silberstein S.
    Characterization of the B-Raf interactome in mouse hippocampal neuronal cells.
    Journal of Proteomics 74:186-198 (2011)
  • Bonfiglio J.J., Inda, C., Refojo, D., Holsboer F., Arzt E., Silberstein S.
    The Corticotropin Releasing Hormone network and the Hypothalamic-Pituitary-Adrenal axis: molecular and cellular mechanisms involved.
    Neuroendocrinology 94:12-20 (2011)
  • Silberstein, S., Vogl, A.M., Refojo, D., Senin, S.A., Wurst, W. , Holsboer, F., Deussing, J.M., Arzt, E.
    Amygdaloid pERK1/2 in Corticotropin-Releasing Hormone overexpressing mice under basal and acute stress conditions.
    Neuroscience 159:610-617 (2009)
  • Silberstein S, Vogl AM, Bonfiglio JJ, Wurst W, Holsboer F, Arzt E, Deussing JM, Refojo D.
    Immunology, signal transduction and behavior in HPA axis-related genetic mouse models.
    Ann N Y Acad Sci 1153:120-30 (2009)