Macromolecular Transfer from Glia to the Axon
Authors: Lasek Raymond J. , Tytell Michael A. 
Published: April 2021

Axons do not contain polysomes and therefore are unable to synthesize proteins. On the other hand, the nerve cell body has a well-developed protein synthesizing capacity, and proteins are conveyed into the axon from the cell body by orthograde axonal transport. Studies on vertebrate neurones demonstrate that the proteins conveyed from the cell body constitute all of the major structures of the axon including : membranous vesicles, the endoplasmic reticulum, mitochondria, and the cytoskeleton which consists of microtubules, neurofilaments, and microfilaments. Although the nerve cell body is the major source of the macromolecules which provide the structural integrity of the axon, in some axons the glial cells surrounding the axon also supply proteins to the axon. The transfer of newly synthesized proteins from glial cells to the axon is documented most completely in the case of the squid giant axon. The transfer of proteins from glial cells to the neurone can be studied in the giant axon by incubating axons, which have been disconnected from their nerve cell bodies, in a solution which contains labelled amino acids. The glial cells transfer as much as 40 % of their newly synthesized proteins to the giant axon. These transferred proteins can be studied in axoplasm which is separated from the giant axon by extrusion.

What are the comparative roles of proteins supplied to the axon by the glial cells and the nerve cell body? To begin to answer this question, we have compared the glial-transfer proteins with the proteins which constitute whole axoplasm. The proteins were analysed by two-dimensional polyacrylamide gel electrophoresis, and axoplasmic proteins were detected by staining the gels with Coomassie blue, whereas the labelled proteins were detected by fluorography of the same gels. The glial-transfer proteins differ substantially from the stained axoplasmic proteins. For example, neurofilament proteins and tubulin are major proteins of the axoplasm but are not represented among the labelled proteins which are transferred from the glial cells. In fact, these proteins are not synthesized to any significant degree by the glial cells. One of the glial-transfer proteins (molecular weight 70000) stands out because it is heavily labelled and is well resolved on the gels. This protein which we have named traversin is present among the stained proteins of whole axoplasm but is a relatively minor component of the axoplasm. In order to determine whether traversin is supplied to the axon by the nerve cell body we analyzed the proteins synthesized in the stellate ganglion which contains the nerve cell bodies of the giant axon. The pattern of proteins synthesized by the stellate ganglion was similar to that of whole axoplasm, but was very different from the constellation of proteins transferred from the glial cells. Traversin was not among the major labelled proteins synthesized by the ganglion and is at most a minor synthetic product of the ganglion. Because the ganglion contains glia, we can not ascertain whether the small amount of labelled traversin in the ganglion was synthesized in the glia or the nerve cell bodies. However, these results suggest that traversin is synthesized in much greater amounts by glial cells than by nerve cells. If, as our results suggest, traversin is supplied to the axon principally by the glial cells, then the proteins transferred from the glial cells are likely to be specialized in function and not simply an accessory source which supplements the proteins supplied by the nerve cell body.

Although some of the proteins transferred from the glial cells are special and are probably not supplied to the axon by the nerve cell body, we have also found proteins which are supplied by both the nerve cell body and the glial cells. One of these proteins is actin. The presence of actin in the population of proteins which are transferred from the glial cells is particularly interesting because of the known contractile function of this protein. Actin could be involved in the mechanism of protein transfer from the glial cells. The transferred proteins apparently exist in the form of a complex in the axoplasm. This complex of proteins can be separated from axoplasm because of its chromatographic behaviour of Sephadex G-200. These results suggest that the glial-transfer proteins are conveyed from the glial cell to the axon in the form of a particle which includes actin in its structure.