Emx2 homeodomain transcription factor interacts with eukaryotic translation initiation factor 4E (eIF4E) in the axons of olfactory sensory neurons.
We report that Emx2 homeogene is expressed at the mRNA and protein levels in the adult mouse olfactory neuroepithelium. As expected for a transcription factor, Emx2 is present in the nucleus of immature and mature olfactory sensory neurons. However, the protein is also detected in the axonal compartment of these neurons, both in the olfactory mucosa axon bundles and in axon terminals within the olfactory bulb. Emx2 axonal staining is heterogeneous, suggesting an association with particles. Subcellular fractionations of olfactory bulb synaptosomes, combined with chemical lesions of olfactory neurons, confirm the presence of Emx2 in axon terminals. Significant amounts of Emx2 protein cosediment with high density synaptosomal subfractions containing eukaryotic translation initiation factor 4E (eIF4E). Nonionic detergents and RNase treatments failed to detach eIF4E and Emx2 from these high-density fractions enriched in vesicles and granular structures. In addition, Emx2 and eIF4E can be coimmunoprecipitated from olfactory mucosa and bulb extracts and interact directly, as demonstrated in pull-down experiments. Emx2 axonal localization, association with high-density particles and interaction with eIF4E strongly suggest that this transcription factor has new nonnuclear functions most probably related to the local control of protein translation in the olfactory sensory neuron axons. Finally, we show that two other brain-expressed homeoproteins, Otx2 and Engrailed 2, also bind eIF4E, indicating that several homeoproteins may modulate eIF4E functions in the developing and adult nervous system.
Nédélec
Stéphane
S
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8542, Neuropharmacology and Development, Ecole Normale Supérieure, 46 Rue d'Ulm, 75005 Paris, France.
Foucher
Isabelle
I
Brunet
Isabelle
I
Bouillot
Colette
C
Prochiantz
Alain
A
Trembleau
Alain
A
D000818:Animals; D001369:Axons / Q000378:metabolism*; D019556:COS Cells; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D051857:Otx Transcription Factors; D011485:Protein Binding; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism; D013574:Synaptosomes / Q000737:chemistry / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099266:Engrailed 2 Protein; D000099260:Empty Spiracles Homeobox Proteins
D039561:Eukaryotic Initiation Factor-4E; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099266:Engrailed 2 Protein; D000099260:Empty Spiracles Homeobox Proteins; C497659:OTX2 protein, human; C497660:Otx2 protein, mouse