Astrocytes, the major glial population in the central nervous system (CNS), play an important role in neuronal homeostasis, neurogenesis, and synaptogenesis. The cells have a stellate shape with elaborated processes in the developing CNS. Cultured astrocytes become stellate when the cells undergo differentiation in response to stimuli. Nevertheless, the molecular mechanism for astrocytic stellation is poorly understood. Here, we showed that the addition of serum induced a flat polygonal shape in cultured astrocytes with a reduced level of Mps one binder 2 (Mob2) that is involved in neurite growth by forming stable complex with a nuclear Ser/Thr kinase Dbf2-related protein kinase 1 (NDR1). Furthermore, exposure to a membrane permeable cAMP analogue, dbcAMP, not only induced astrocytic stellation, but also caused an increase in Mob2 expression. Similarly, the upregulation of Mob2 mRNA expression was induced by exposure of astrocytes to pituitary adenylyl cyclase-activating polypeptide (PACAP). Pretreatment with a cAMP/protein kinase A (PKA) inhibitor, KT-5720, significantly blocked the effect of dbcAMP and PACAP on induced upregulation of Mob2 mRNA expression in astrocytes. In addition, the process withdrawal of dbcAMP-treated astrocytes was caused by the inhibition of Mob2 expression using lentivirus-mediated Mob2 shRNA delivery system. Based on our findings, we suggest that Mob2 is involved in PKA signaling-mediated astrocytic stellation.
Copyright © 2012 Wiley Periodicals, Inc.