Mps one binder 2 gene upregulation in the stellation of astrocytes induced by cAMP‐dependent pathway

Abstract

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.

Profilin Isoforms Modulate Astrocytic Morphology and the Motility of Astrocytic Processes

“…Co-application of the cAMP raising with a competitive inhibitor may diminish its effectiveness [ 50 ], especially since cerebellar astrocytes are most susceptible to cAMP induced stellation [ 51 ]. Another recent study describes KT5720 as effective inhibitor of astrocytic stellation [ 52 ], which is in line with our results. The aforementioned study by Perez and colleagues [ 49 ] furthermore suggests of short time inactivation of PI3K upon forskolin treatment.…”

MOB2 suppresses GBM cell migration and invasion via regulation of FAK/Akt and cAMP/PKA signaling

“…Our data from Fig. 6b indicated that FSK stimulation increased MOB2 levels in GBM cells, consistent with a previous study reporting that Mob2 expression in stellate astrocytes was regulated by cAMP/PKA-dependent pathway 32 . We extended and confirmed FSK-induced MOB2 expression in additional three GBM cell lines including Hs863, LN18, and U87MG (Fig.…”

MOB (Mps one Binder) Proteins in the Hippo Pathway and Cancer

“…MOB2 loss-of-function impairs the correct neuronal positioning within the developing cortex, thereby associating MOB2 inactivation with a disorder such as periventricular nodular heterotopia [114]. Moreover, MOB2 plays a part in PKA-mediated signalling in astrocytes [176]. Similarly, MOB2 plays a neurological function in invertebrates, since dMOB2 expression is necessary and sufficient to regulate the growth of larval neuromuscular junctions in flies [23].…”