INITIAL CHARACTERIZATION OF ANOSMIN-1, A PUTATIVE EXTRACELLULAR-MATRIX PROTEIN SYNTHESIZED BY DEFINITE NEURONAL CELL-POPULATIONS IN THE CENTRAL-NERVOUS-SYSTEM

The KAL gene is responsible for the X-chromosome linked form of Kallma nn's syndrome in humans, Upon transfection of CHO cells with a human K AL cDNA, the corresponding encoded protein, KALc, was produced, This p rotein is N-glycosylated, secreted in the cell culture medium, and is localized at the cell surface, Several lines of evidence indicate that heparan-sulfate chains of proteoglycan(s) are involved in the binding of KALc to the cell membrane, Polyclonal and monoclonal antibodies to the purified KALc were generated, They allowed us to detect and chara cterize the protein encoded by the KAL gene in the chicken central ner vous system at late stages of embryonic development, This protein is s ynthesized by definite neuronal cell populations including Purkinje ce lls in the cerebellum, mitraI cells in the olfactory bulbs and several subpopulations in the optic tectum and the striatum. The protein, wit h an approximate molecular mass of 100 kDa, was named anosmin-1 in ref erence to the deficiency of the sense of smell which characterizes the human disease, Anosmin-1 is likely to be an extracellular matrix comp onent. Since heparin treatment of cell membrane fractions from cerebel lum and tectum resulted in the release of the protein, we suggest that one or several heparan-sulfate proteoglycans are involved in the bind ing of anosmin-1 to the membranes in vivo.