title: PKCε and allopregnanolone: functional cross-talk at the GABAA receptor level.
abstract: Changes in GABAergic inhibition occur during physiological processes, during response to drugs and in various pathologies. These changes can be achieved through direct allosteric modifications at the γ-amino butyric acid (GABA) type A (GABAA) receptor protein level, or by altering the synthesis, trafficking and stability of the receptor. Neurosteroids (NSs) and protein kinase C (PKC) are potent modulators of GABAA receptors and their effects are presumably intermingled, even though evidence for this hypothesis is only partially explored. However, several PKC isoforms are able to phosphorylate the GABAA receptor, producing different functional effects. We focused on the ε isoform, that has been correlated to the sensitivity of the GABAA receptor to allosteric modulators and whose expression may be regulated in peripheral sensory neurons by NSs. The cross-talk between PKC-ε and NSs, leading to changes in GABAA receptor functionality, is considered and discussed in this perspective.
authors: Department of Life Science, University of Modena and Reggio Emilia Modena, Italy.
authors: Giulia
authors: G
authors: Puia
authors: Department of Life Science, University of Modena and Reggio Emilia Modena, Italy.
authors: Federica
authors: F
authors: Ravazzini
authors: Department of Pharmacological and Biomolecular Sciences, University of Milan Milan, Italy.
authors: Luca Franco
authors: LF
authors: Castelnovo
authors: Department of Pharmacological and Biomolecular Sciences, University of Milan Milan, Italy.
authors: Valerio
authors: V
authors: Magnaghi
keywords: GABAA receptor; PKCepsilon; neurosteroids; phosphorylation site; receptor traffiking