Receptors for insulin-like growth factor (IGF)-II/cation-independent mannose-6-phosphate are present in mouse neurons and influenced by IGF-II treatment

We investigated the cellular and subcellular localization of IGF-II receptors in the adult mouse central nervous system (CNS). The IGF-II receptor and the cation-independent (Cl) mannose-6-phosphate (M6P) receptor are identical. Immunohistochemistry demonstrated that IGF-II/Cl-M6P receptor immunoreactivity was mostly restricted to middle- to large-sized neurons throughout the CNS. A small number of glial cells were weakly to moderately labeled. IGF-II/Cl-M6P receptor immunoreactivity was largely recognized within endosome-lysosomal structures in the neurons by immunoelectron microscopy (EM) of the CNS tissues. More intense labeling was observed in larger neurons that included more abundant endosome-lysosomal structures, indicating that IGF-II/Cl-M6P receptor immunoreactivity reflects the endosome-lysosomal activity specifically present in neurons. These results are consistent with the general assumption that IGF-II/Cl-M6P receptors are involved in sorting lysosomal enzymes within cells. IGF-II/Cl-M6P receptors also endocytose secreted IGF-II and M6P-containing glycoproteins as scavenger receptors. Furthermore, it has been reported that they are involved in the development of transmembrane IGF-II signals. Therefore, we next tried to determine if they are expressed on the cell surface of primary cultured cortical neurons. By immunofluorescence and immuno-EM, particularly by immunoscanning EM, expression of IGF-II/Cl-M6P receptors was demonstrated in the neuronal cell surface in response to IGF-II treatment.