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.
Di Nardo
Ariel A
AA
CNRS UMR 8542, Développement et Neuropharmacologie, Ecole Normale Supérieure, 46 rue d'Ulm, 75005 Paris, France.
Nedelec
Stéphane
S
Trembleau
Alain
A
Volovitch
Michel
M
Prochiantz
Alain
A
Montesinos
Maria Luz
ML
D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004622:Embryo, Mammalian; D015870:Gene Expression / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization / Q000379:methods; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D009474:Neurons / Q000166:cytology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013574:Synaptosomes / Q000378:metabolism
C080330:En1 protein, mouse; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins