Evidence for Developmentally Regulated Local Translation of Odorant Receptor mRNAs in the Axons of Olfactory Sensory Neurons

Abstract

Odorant receptor mRNAs are transported within axons of olfactory sensory neurons that project into the olfactory bulb. Odorant receptor proteins have been identified along the distal part of these axons, which raises the possibility of their local synthesis in axons. We took advantage of the anatomical separation between the olfactory mucosa (which contains the sensory neuron cell bodies) and the bulb (which contains sensory axons but no sensory neuron cell bodies) to address this issue using a quantitative biochemical approach. Combining a method that separates polysome-associated mRNAs from untranslated mRNAs with a reverse transcription-quantitative PCR approach, we demonstrate that significant amounts of odorant receptor mRNAs are associated with polysomes in the sensory axons of the adult mouse bulb. We thus provide the first evidence for local synthesis of odorant receptor proteins in these axons. Interestingly, the rate of odorant receptor mRNA translation in axons is significantly greater during periods when the proportion of immature axons is higher (i.e., at postnatal day 4 or on regeneration after chemical lesion in adults). In contrast, the olfactory marker protein mRNA, which is restricted to mature axons, is translated at a low and constant level. Overall, we demonstrate that translation levels of odorant receptor mRNAs in axons are developmentally regulated, and positively correlated to the stage of axonal growth into the bulb. Given the established function of odorant receptors in the axonal wiring of sensory projections, we propose that this regulated axonal translation may play a role in the development and maintenance of the glomerular array.

Principles and roles of mRNA localization in animal development

“…For example, translation of EphA2 guidance receptor mRNA reporter constructs is activated in chick spinal cord axons only once commissural growth cones have crossed the midline (Brittis et al, 2002). Also consistent with developmental regulation of axonal protein synthesis in vivo, local translation of mouse odorant receptor mRNAs is higher in immature than in adult olfactory bulbs (Dubacq et al, 2009). …”

Targeting Axonal Protein Synthesis in Neuroregeneration and Degeneration

“…Indeed, recent results from carefully designed in vivo studies are beginning to change the assumption that mature axons are translationally inactive. For example, odorant receptor mRNAs are translated within axons at a high rate in immature axons but, importantly, the transcript coding for the olfactory marker protein, a protein specific to mature axons, is also translated within axons, albeit at a much lower level [25]. Further, a transgene mRNA containing the 3'untranslated region (UTR), that is the regulatory region, of β-actin mRNA localizes to and appears to be translated within axons of peripheral and central nervous system neurons in mice even well after neurodevelopment has been completed [26].…”

Axonal commissures in the central nervous system: how to cross the midline?

“…However, the olfactory system has provided one of the nicest examples, with mRNAs encoding odorant receptors, which are then transported in olfactory axons and later associate with polysomes in sensory axons of the olfactory bulb [89]. These experiments were carried out in the adult, but olfactory connections are continuously renewed, strongly suggesting that immature axons contain these mRNAs.…”