Journal of Neuroscience, Vol 4, 1830-1839, Copyright © 1984 by Society for Neuroscience
Analysis of the apparent biphasic axonal transport kinetics of fucosylated glycoproteins
JF Goodrum and P Morell
Following intraocular injection of [3H]fucose, which labels many
glycoproteins of retinal ganglion cells, the accumulation of transported
radioactivity arriving at the superior colliculus (nerve terminals) peaks
within a few hours and decays with a time course of hours. Then, over a
period of several days, radioactivity again accumulates at the superior
colliculus and then decays with a half-life of days. The second peak also
represents fast transported material since it occurs almost simultaneously
along the optic nerve and tract as well as at the nerve endings. Such data
have been interpreted as evidence for both a group of rapidly released,
rapidly transported glycoproteins (first peak) and a group of slowly
released but rapidly transported glycoproteins (second peak). We
investigated this supposition by studying in more detail the metabolism of
some individual fucosylated proteins in both the retina and superior
colliculus. We noted that much of the radioactivity incorporated in
fucosylated glycoproteins at the retina was rapidly metabolized (with a
turnover on the order of hours), while the remainder of the fucosylated
moieties had a metabolic half-life on the order of days. This was also true
of the metabolic behavior of several individual glycoproteins, selected for
study because they are major components of the group committed to transport
and accumulating in two waves at the superior colliculus. In other
experiments we injected [35S]methionine intraocularly and examined the
metabolism in the retina and the kinetics of transport to the superior
colliculus of the peptide backbone of these same individual proteins. In
contrast to the two waves of accumulation of radioactivity from [3H]fucose,
accumulation of radioactivity of the peptide backbone of the same
glycoproteins was monophasic. Our explanation of these data involves the
presence of two types of fucose moieties on the peptides. One group of
fucose moieties is labile and is lost from the peptide backbone over a
period of hours. Other fucose moieties are approximately as metabolically
stable as the peptide backbones to which they are attached. The actual
peptide backbones of the glycoproteins are committed to rapid transport
over a period of several days. Thus, the first (and most prominent) peak of
transported radioactivity in [3H]fucosylated glycoproteins does not
represent a discrete phase of transport but, rather, is the summation of
kinetics of gradual arrival of proteins and the rapid drop in their
specific radioactivity as the more labile moieties of [3H]fucose are
lost.(ABSTRACT TRUNCATED AT 400 WORDS)