Expression of the AMF/neuroleukin receptor in developing and adult brain cerebellum

The peptide sequence of autocrine motility factor (AMF), a tumor secreted c ytokine that induces cell motility, corresponds to that of the previously i dentified cytokine/ enzyme, neuroleukin/glucose-6-phosphate isomerase. Neur oleukin is a neurotrophic factor that promotes neuronal survival and sprout ing at the neuromuscular junction. The AMF receptor (AMF-R) has been identi fied and shown to be highly expressed in malignant tumors with minimal expr ession in adjacent normal tissue. Neuroleukin mRNA is highly expressed in t he cerebellum and we therefore undertook a developmental study of AMF-R exp ression in rat cerebellum. As determined by immunoblot, AMF-R is expressed at equivalent high levels in brain and cerebellum of postnatal day 5 (P5) a nd 12 (P12) rats and at significantly reduced levels in the adult. Co-immun ofluorescence studies with MAP-2 and gamma-actin revealed that at P12, AMF- R was mainly localized to Purkinje and granule cells. Moreover, the premigr atory cells of the external granular layer were also immunoreactive for AMF -R suggesting a role for AMF-R in granule cell migration during cerebellar development in the first two weeks after birth. In the adult, AMF-R distrib ution was similar to P12, although weaker, and was localized to Purkinje an d granule cells. AMF-R labeling of GFAP positive glial processes could not be detected in cerebellar sections although in cerebellar primary cultures, both neurons and glial cells were labeled for AMF-R. In neurons, AMF-R lab eling was present in the cell body, neurites and growth cones. These data i ndicate that regulation of the neurotrophic function of neuroleukin might b e regulated spatially and temporally by expression of its receptor, AMF-R, in developing and adult cerebellum. (C) 2000 Wiley-Liss, Inc.