Immunohistochemical distribution of cation-dependent mannose 6-phosphate receptors in the mouse central nervous system: comparison with that of cation-independent mannose 6-phophate receptors

Most mammalian cells express two types of mannose 6-phosphate (M6P) receptors (MPRs), which are involved in the sorting of lysosomal enzymes within the cells. They are referred to as cation-dependent (CD-) MPR and cation-independent (CI-) MPR/insulin-like growth factor II receptor (IGF-IIR), based on their divalent cation requirements and the ability to bind IGF-II. The complementary actions of these two related but distinct MPRs in the sorting function suggest that they have different immunohistochemical distributions. To address this issue, we investigated the cellular distribution of CD-MPR immunoreactivity in the adult mouse central nervous system (CNS), and compared it with that of CI-MPR/IGF-IIR immunoreactivity, which we had previously investigated. These two immunoreactivities were localized in neurons of the CNS, with more intense labeling in the medial septal nucleus, the nucleus of the Broca's diagonal band, layers IV-VI of the cerebral neocortex, layers II-III of the entorhinal cortex, the habenular nucleus, the median eminence, several nuclei and structures of the brainstem, the Purkinje cell layer of the cerebellum, and in the ventral horn of the spinal cord. Although intense immunoreactivities of both MPRs were observed in the same groups of neurons in the same regions, the spatial differences in immunoreactive intensity for CI-MPR/IGF-IIR were greater, particularly in the telencephalon such as the basal forebrain and cerebral cortex, than those for CD-MPR. These findings suggest that CD-MPR is ubiquitously necessary for the general function of neurons, whereas CI-MPR/IGF-IIR is selectively necessary for certain region- and neurotransmitter-specific functions of neurons.