Maf1 regulates dendritic morphogenesis and influences learning and memory.

Maf1, a general transcriptional regulator and mTOR downstream effector, is highly expressed in the hippocampus and cortex, but the function of Maf1 in neurons is not well elucidated. Here, we first demonstrate that Maf1 plays a central role in the inhibition of dendritic morphogenesis and the growth of dendritic spines both in vitro and in vivo. Furthermore, Maf1 downregulation paradoxically leads to activation of AKT-mTOR signaling, which is mediated by decreased PTEN expression. Moreover, we confirmed that Maf1 could regulate the activity of PTEN promoter by luciferase reporter assay, and proved that Maf1 could bind to the promoter of PTEN by ChIP-PCR experiment. We also demonstrate that expression of Maf1 in the hippocampus affects learning and memory in mice. Taken together, we show for the first time that Maf1 inhibits dendritic morphogenesis and the growth of dendritic spines through AKT-mTOR signaling by increasing PTEN expression.