Uniform distribution and similar turnover rates of individual gangliosides along axons of retinal ganglion cells in the chicken

The axonal transport of proteins, glycoproteins, and gangliosides in sensory neurons of the sciatic nerve was examined in adult rats exposed to acrylamide via intraperitoneal injection (40 mg/kg of body weight/day for nine consecutive days). The L5 dorsal root ganglion was injected with either [35S]methionine to label proteins or [3H]glucosamine to label, more specifically, glycoproteins and gangliosides. At times ranging from 2 to 6 h later, the sciatic nerve and injected ganglion were excised and radioactivity in consecutive 5-mm segments determined. In both control and acrylamide-treated animals, outflow profiles of [35S]methionine-labeled proteins showed a well defined crest which moved down the nerve at a rate of approximately 340 mm/day. Similar outflow profiles and transport rates were seen for [3H]glucosamine-labeled glycoproteins in control animals. However, in animals treated with acrylamide, the crest of transported labeled glycoprotein was severely attenuated as it moved down the nerve. This finding suggests that in acrylamide-treated animals, axonally transported glycoproteins were preferentially transferred (unloaded or exchanged against unlabeled molecules) from the transport vector to stationary axonal structures. We also examined the clearance of axonally transported glycoproteins distal to a ligature on the nerve. The observed impairment of clearance in acrylamide-treated animals relative to controls is supportive of the above hypothesis. Acrylamide may directly affect the mechanism by which axonally transported material is unloaded from the transport vector. Alternatively, the increased rate of unloading might reflect an acrylamide-induced increase in the demand for axonally transported material.

Section: Discussionmentioning

confidence: 99%

Acrylamide‐Induced Increases in Deposition of Axonally Transported Glycoproteins in Rat Sciatic Nerve

Harry

Goodrum

Bouldin

et al. 1989

“…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. In view of the presumed biological significance of these macromolecules (for reviews, see Margolis and Margolis, 1977;Ledeen et al, 1981;Markwell et al, 1981;Ando, 1983), a fuller description of the transport of these glycoconjugates appears appropriate.…”

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.

“…This contrasts with the hypothesis that gangliosides are preferentially localized in nerve endings (Hansson et al, 1977). The former suggestion is supported by studies in the visual system of the rabbit (Ledeen et al, 1981), chicken (Rosner and Merz, 1982), and rat (Gammon et al, 1985) which indicate that a substantial amount of transported ganglioside is retained in axons (optic tract). This situation is different from that for glycoproteins, which appear to be transported preferentially to nerve endings (Karlsson and Sjostrand, 197 1;Droz et al, 1973;Gammon et al, 1985).…”

Section: Discussionmentioning

confidence: 90%

“…48, (1987. In the visual system, gangliosides synthesized by retinal ganglion cells from intraocularly injected sugars are rapidly transported to the nerve endings of the optic pathway (Forman et al, 197 1;Forman and Ledeen, 1972;Rosner, 1975;Ledeen et al, 1976Ledeen et al, , 1981Landa et al, 1979;Rosner and Merz, 1982;Gammon et al, 1985). Studies that employed nerve ligation techniques to examine ganglioside transport in the peripheral nervous system demonstrated an accumulation of radioactive gangliosides proximal to sciatic nerve ligature following injection of labeled precursors into the dorsal root ganglion (DRG) or the ventral spinal cord (Yates et al, 1984;Aquino et al, 1985a,b).…”

mentioning

confidence: 99%

Axonal Transport Characteristics of Gangliosides in Sensory Axons of Rat Sciatic Nerve

Gj¹,

Jf²,

et al. 1987

The distribution of axonally transported gangliosides and glycoproteins along the sciatic nerve was examined from 3 h to 4 weeks following injection of[3H]glucosamine into the fifth lumbar dorsal root ganglion of adult rats. Incorporation of labeled precursor into these glycoconjugates reached a maximal level in the ganglion within 6 h. Outflow patterns of radioactivity for glycoproteins showed a well-defined crest with a transport rate of approximately 330 mm/day. In contrast, the crest of transported gangliosides was continuously attenuated, implying a significant deposition along the axon, and an alternative method of calculating velocity was required. Analysis of accumulation of labeled material at double ligatures demonstrated both anterograde and retrograde transport of glycoproteins and gangliosides and allowed for the calculation of an anterograde transport rate of about 270 mm/day for each. Additional evidence of ganglioside transport is provided in that the TLC pattern of transported radioactive gangliosides accumulating at a ligature is significantly different from the pattern seen in the dorsal root ganglion or following intraneural administration of the labeled precursor. These data indicate that gangliosides are transported at the same rapid rate as glycoproteins but are subject to a more extensive exchange with stationary material than are glycoproteins.