ReviewFunction and translational regulation of mRNA in developing axons
Introduction
Work over the last three decades has established the existence of protein translation machinery and mRNAs in axons of both vertebrates and invertebrates (for a review see [1]). However, while dendritic protein translation is generally accepted [2], axonal protein translation in vertebrates has remained somewhat controversial. This difference might be explained, in part, by early work in the mature nervous system that appeared to show a lack of protein translation machinery in axons [3]. In contrast, more recent studies indicate that, during development, axons contain mRNAs and ribosomes. Here, we discuss the differences in translational capacity between developing and mature vertebrate axons. We also address emerging signaling pathways that regulate translation in developing axons. But first, we focus on the phenomenon of local translation in neurons and other cell types, and potential rationales for its occurrence in developing axons.
Section snippets
The role of local protein synthesis in developing axons
While protein translation in developing axons is an intensively studied phenomenon [4], [5], [6], [7], [8], [9], its purpose and function is far less clear. Often, it is argued that the extreme distance between the soma and the tips of axons, along with the slow rate of transport of proteins from the soma to axons make local protein synthesis in axons necessary (e.g. [10]). In this view, local translation is understood simply as a means to overcome the slow anterograde transport from the cell
Changes in translational capacity during axonal maturation
The translational capacity of axons is temporally regulated during neuronal development. mRNAs and ribosomal RNA levels in developing axons of vertebrates are appreciably high but RNA levels decline during development and can no longer be detected in axons of cultured hippocampal neurons by 10 days in vitro [12]. A few mRNAs have been found in some specialized mature neurons: hypothalamic magnocellular neurons axons contain the mRNAs encoding the neurohypophyseal hormone precursors of
Techniques to study local protein translation
To study the regulation of local translation in axons it is necessary to detect translation events with spatial and temporal precision. The study of local translation in axons has been greatly enhanced by the use of fluorescent reporter methods, such as the membrane-anchored, destabilized enhanced GFP (dEGFP) reporter. This method was first used to monitor local protein translation of CaMKIIα in dendrites [54]. The usefulness of this reporter derives from the presence of a destabilization
Conclusion
Developing axons are able to respond and adapt to their environment by local protein translation and degradation without the direct involvement of the nucleus. The capacity to synthesize proteins locally is greatly reduced or even completely lost once axons mature, but it can be regained in regenerating axons. Impaired restoration of local translation might contribute to impaired re-growth of axons following axonal injury. The understanding of the mechanisms governing the capability of local
Acknowledgements
U. Hengst is supported by the Paralysis Project of America. S.R. Jaffrey is supported by the Fragile X Research Foundation (FRAXA) and NIMH. We are grateful to L.J. Cox for comments on the manuscript. The authors apologize for omitting many primary references due to space limitations.
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