Axonal transport of proteins and glycoproteins in the rat nigro-striatal pathway and the effects of 6-hydroxydopamine

Following intraocular injection of [3H]fucose in the rat, radioactive glycoproteins are rapidly transported to the nerve terminals in at least two waves, one with a peak at 8 h and a second with a peak at about a week. The molecular weight distribution of radioactive peptides in ach transport wave as determined by gel electrophoresis in buffers containing sodium dodecyl sulfate is very similar. Most of the many glycopeptides in the first wave of rapid transport pass through the optic tract in unison (apparent half‐life of about 15 h) and are preferentially destined for the nerve endings. However, two proteins of apparent M. W. 28,000 and 49,000 are preferentially retained in the axons. The remaining proteins, after reaching the nerve endings (superior colliculus), decay with apparent half‐lives ranging from 17 to 34 h. During the second wave a large amount of the 28,000 and 49,000 M. W. peptides are again preferentially retained in the axons. The remaining proteins, on reaching the nerve endings, decay with apparent half‐lives ranging from 5 to 9 days. Subcellular fractionation of the superior colliculus supports the hypothesis that the 49,000 and 28,000 M. W. peptides are the predominantly labeled glycoproteins present in myelinated axons (representing over 50% of the radioactive glycoproteins 7 days following injection), although they are probably also present in membranes of the nerve endings. A comparison with glycoprotein transport in other tracts (geniculocortical and nigrostriatal tracts) suggests that glycoprotein transport in these pathways has many similarities to glycoprotein transport in the retinal ganglion cells, and that the optic system is a good general model for axonal transport in the CNS.

Section: Methodsmentioning

confidence: 99%

Axonal Transport, Deposition, and Metabolic Turnover of Glycoproteins in the Rat Optic Pathway

Goodrum

Morell

1982

“…It has long been known that glycoproteins are transported rapidly. The time course of this process, as well as the molecular-weight distribution of the transported fucosylated glycoproteins, has been described in some detail for several pathways in a number of species (Bondy and Madsen, 1971;Forman et al, 1971;Karlsson and Sjostrand, 1971;McEwen et al, 1971;Edstrom and Mattsson, 1972;Ochs, 1972;Ambron et al, 1974; Padilla and Morell, 1 9 8 0~; Roger et al, 1980;Toews et al, 1982;Goodrum and Morell, 1982;Stone et al, 1983). Although less is known about the transport of other biologically significant glycoconjugates, it is clear that gangliosides (Forman and Ledeen, 1972;Rosner and Merz, 1982) and glycosoaminoglycans (GAGs) (Elam and Agranoff, 1971;Elam and Peterson, 1976;Goodrum et al, 1979;Elam, 1982) are also transported from the cell body to nerve endings.…”

mentioning

confidence: 99%

Axonal Transport of Glycoconjugates in the Rat Visual System

Gammon¹,

Goodrum²,

Toews³

et al. 1985

Long-Evans rats at 45 days of age were injected intraocularly with 25 mu Ci of [3H]glucosamine. Incorporation of radioactivity into retinal gangliosides, glycoproteins, and glycosaminoglycans (GAGs) was determined at various times after injection. Portions of all three classes of radioactive macromolecules were committed to rapid axonal transport in the retinal ganglion cells. With respect to gangliosides about 60% of those synthesized in the retina were retained in that structure, 30% were committed to transport to regions containing the nerve terminal structures (lateral geniculate body and superior colliculus), and about 10% were deposited in stationary structures of the axons (optic nerve and tract). With the exception of ganglioside GD3 the molecular species distribution of gangliosides synthesized in the retina matched that committed to transport. In contrast to gangliosides a smaller fraction of newly synthesized retinal glycoprotein (less than 12% of that synthesized in the retina) was committed to rapid transport to nerve ending regions and only about 0.5% was retained in the nerve and tract. The molecular-weight distribution of glycoproteins committed to transport differed quantitatively from that of the retina. With respect to GAGs an even smaller portion (1-2%) of that synthesized in the retina was committed to rapid transport; of this portion almost all was recovered in nerve terminal-containing structures. A constant proportion of each retinal GAG species was transported to the superior colliculus. We suggest that most of the retinal gangliosides are synthesized in neurons and preferentially in ganglion cells (possibly a function of the large surface membrane area supported by these cells). Subcellular fractionation experiments indicated that transported gangliosides, glycoproteins, and GAGs may be preferentially distributed into different subcellular compartments.

“…The movement of proteins from the nerve cell body toward the nerve endings has been extensively investigated in both the CNS and the PNS (for reviews, see Schwartz, 1979; Grafstein and Forman, 1980). Studies specifically of glycoprotein transport have been conducted primarily in the visual system (for example, Karlsson and Sjostrand, 1971;Specht and Grafstein, 1977;Goodrum et al, 1979;Goodrum and Morell, 1982) and in other cranial nerves DiGiamberardino et al, 1973;Frizell and Sjostrand, 1974;Elam and Peterson, 1979;Tytell et al, 1980), although several other tracts located entirely within the CNS have also been investigated (Levin, 1977;Padilla and Morell, 1980;Roger et al, 1980). Fucosylated glycoproteins are rapidly transported, primarily as particulate material, and are destined primarily for nerve endings (for reviews, see Elam, 1979;Grafstein and Forman, 1980).…”

mentioning

confidence: 99%

Axonal Transport and Metabolism of Glycoproteins in Rat Sciatic Nerve

Toews

Saunders

Morell

1982

The axonal transport and metabolism of glycoproteins in sciatic nerve sensory axons were examined from 2 h to 7 weeks following injection of [3H]fucose into the 5th lumbar dorsal root ganglion of adult rats. Incorporation of fucose into glycoproteins was prolonged; only half of the 3H label in the ganglion was acid‐insoluble after 4 h, and maximal labeling did not occur until approximately 24 h after injection. [3H]Glycoproteins were transported distally at a rate of approximately 310 mm per day after a synthesis and/or processing lag of approximately 40 min. Gel electrophoresis demonstrated that many glycoproteins were transported, including prominent labeled species having apparent M.W. of approximately 49,000, 90,000, 118,000, and 132,000. With increasing time after injection, a peak with an apparent M.W. of 49,000 accounted for an increasing proportion of the total label in the nerve. The accumulation of this glycoprotein (possibly a subunit of Na+,K+‐ATPase, an enzyme known to be present in axolemma) was due in part to its preferential deposition in the axons, while other glycoproteins passed through the axons directly to the nerve terminals. Radioactivity in another labeled glycoprotein, with an apparent M.W. of 30,000, also increased preferentially in the nerve relative to other labeled glycoproteins. This was shown to be the myelin P0 protein. This protein was not transported from the ganglion; rather, its increased prominence with time in the nerve was due both to a decrease in amounts of other labeled species and to an absolute increase in labeling of the P0 protein, possibly due to reutilization by the Schwann cells of fucose released during turnover of labeled glycoproteins delivered to the axons by axonal transport.