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 CLN3 protein, we expressed CLN3 cDNA in COS-1 and HeLa cell lines. In vitro translation, immunoprecipitation and Western blotting analyses detected an ∼43 kDa polypeptide. Pulse-chase experiments indicated that the CLN3 protein is synthesized as an N-glycosylated single-chain polypeptide, which was not detected in growth medium. Confocal immuno-fluorescence microscopy revealed that the CLN3 protein is localized to the lysosomal compartment. These results provide evidence that Batten disease can be classified as a member of lysosomal diseases.