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- Title
Downregulation of the cAMP/PKA Pathway in PC12 Cells Overexpressing NCS-1.
- Authors
Souza, Bruno R.; Torres, Karen C. L.; Miranda, Débora M.; Motta, Bernardo S.; Caetano, Fernando S.; Rosa, Daniela V. F.; Souza, Renan P.; Giovani, Jr., Antônio; Carneiro, Daniel S.; Guimarães, Melissa M.; Martins-Silva, Cristina; Reis, Helton J.; Gomez, Marcus. V.; Jeromin, Andreas; Romano-Silva, Marco A.
- Abstract
It is well known that dopamine imbalances are associated with many psychiatric disorders and that the dopaminergic receptor D is the main target of antipsychotics. Recently it was shown that levels of two proteins implicated in dopaminergic signaling, Neuronal calcium sensor-1 (NCS-1) and DARPP-32, are altered in the prefrontal cortex (PFC) of both schizophrenic and bipolar disorder patients. NCS-1, which inhibits D internalization, is upregulated in the PFC of both patients. DARPP-32, which is a downstream effector of dopamine signaling, integrates the pathways of several neurotransmitters and is downregulated in the PFC of both patients. Here, we used PC12 cells stably overexpressing NCS-1 (PC12-NCS-1 cells) to address the function of this protein in DARPP-32 signaling pathway in vitro. PC12-NCS-1 cells displayed downregulation of the cAMP/PKA pathway, with decreased levels of cAMP and phosphorylation of CREB at Ser133. We also observed decreased levels of total and phosphorylated DARPP-32 at Thr34. However, these cells did not show alterations in the levels of D and phosphorylation of DARPP-32 at Thr75. These results indicate that NCS-1 modulates PKA/cAMP signaling pathway. Identification of the cellular mechanisms linking NCS-1 and DARPP-32 may help in the understanding the signaling machinery with potential to be turned into targets for the treatment of schizophrenia and other debilitating psychiatric disorders.
- Publication
Cellular & Molecular Neurobiology, 2011, Vol 31, Issue 1, p135
- ISSN
0272-4340
- Publication type
Article
- DOI
10.1007/s10571-010-9562-4