Dendritic Localization and Activity-dependent Translation of Engrailed1 Transcription Factor

Engrailed1 (En1) is a homeoprotein transcription factor expressed throughout adulthood in several midbrain cells, including the dopaminergic neurons of the substantia nigra. Here we report the presence of Engrailed protein and En1 mRNA in proximal dendrites of these neurons and of En1 mRNA in ventral midbrain synaptoneurosomes. We show that the 3' untranslated region of En1 mRNA contains a functional cytoplasmic polyadenylation element (CPE), suggesting that its dendritic localization is regulated by CPE binding protein (CPEB). In order to evaluate activity-regulated translation, conditions were developed using primary midbrain neurons. With this in vitro model, En1 mRNA translation is increased by depolarization in a polyadenylation dependent manner. Furthermore, En1 translation is prevented by rapamycin, implicating the mTOR pathway, which is known to regulate dendritic translation. Together, these results suggest an activity-dependent role for Engrailed in midbrain dopaminergic neuron physiology.