BIOSYNTHESIS AND INTRACELLULAR TARGETING OF THE CLN3 PROTEIN DEFECTIVE IN BATTEN-DISEASE

Batten disease (juvenile-onset neuronal ceroid lipofuscinosis, JNCL), the most common neurodegenerative disorder of childhood, is caused by mutations in a recently identified gene (CLN3) localized to chromosome 16p11.2-12.1. To elucidate the biosynthesis and localization of the C LN3 protein, we expressed CLN3 cDNA in COS-1 and HeLa cell lines. In v itro translation, immunoprecipitation and Western blotting analyses de tected an similar to 43 kDa polypeptide. Pulse-chase experiments indic ated that the CLN3 protein is synthesized as an N-glycosylated single- chain polypeptide, which was not detected in growth medium, Confocal i mmunofluorescence microscopy revealed that the CLN3 protein is localiz ed to the lysosomal compartment. These results provide evidence that B atten disease can be classified as a member of lysosomal diseases.