| 44113 |
abstract |
The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is a multifunctional
transmembrane glycoprotein, which interacts with a number of molecules, including
IGF-II and M6P-containing lysosomal enzymes. The receptor is widely distributed throughout
the brain and is known to be involved in lysosomal enzyme trafficking, cell growth,
internalization and degradation of IGF-II. In the present study, using autoradiographic,
Western blotting and immunocytochemical methods, we provide the first report that
IGF-II/M6P receptors are discretely distributed at all major segmental levels of the
spinal cord and dorsal root ganglia of the adult rat. In the spinal cord, a high density
of [<sup>125</sup>I]IGF-II binding sites was evident in the ventral horn (lamina IX)
and in areas around the central canal (lamina X), whereas intermediate grey matter
and dorsal horn were associated with moderate receptor levels. The dorsal root ganglia
exhibited rather high density of [<sup>125</sup>I]IGF-II binding sites. Interestingly,
meninges present around the spinal cord displayed highest density of [<sup>125</sup>I]IGF-II
binding compared to any given region of the spinal grey mater or the dorsal root ganglia.
Western blot results indicated the presence of the IGF-II/M6P receptor at all major
levels of spinal cord and dorsal root ganglia, with little segmental variation. At
the cellular level, spinal motorneurons demonstrated the most intense IGF-II/M6P receptor
immunoreactivity, followed by interneurons in the intermediate region and deeper dorsal
horn. Some scattered IGF-II/M6P immunoreactive fibers were found in the superficial
laminae of the dorsal horn and dorsolateral funiculus. The meninges of the spinal
cord also seemed to express IGF-II receptor immunoreactivity. In the dorsal root ganglia,
receptor immunoreactivity was evident primarily in a subset of neurons of all diameters.
These results, taken together, provide anatomical evidence of a role for the IGF-II/M6P
receptor in general cellular functions such as transport of lysosomal enzymes and/or
internalization followed by clearance of IGF-II in the spinal cord and dorsal root
ganglia. |