Alessia Calcagni', Leopoldo Staiano, Nicolina Zampelli, Nadia Minopoli, Niculin J Herz, Giuseppe Di Tullio, Tuong Huynh, Jlenia Monfregola, Alessandra Esposito, Carmine Cirillo, Aleksandar Bajic, Mahla Zahabiyon, Rachel Curnock, Elena Polishchuk, Luke Parkitny, Diego Luis Medina, Nunzia Pastore, Peter J Cullen, Giancarlo Parenti, Maria Antonietta De Matteis, Paolo Grumati, Andrea Ballabio
Batten disease, one of the most devastating types of neurodegenerative lysosomal storage disorders, is caused by mutations in CLN3. Here, we show that CLN3 is a vesicular trafficking hub connecting the Golgi and lysosome compartments. Proteomic analysis reveals that CLN3 interacts with several endo-lysosomal trafficking proteins, including the cation-independent mannose 6 phosphate receptor (CI-M6PR), which coordinates the targeting of lysosomal enzymes to lysosomes. CLN3 depletion results in mis-trafficking of CI-M6PR, mis-sorting of lysosomal enzymes, and defective autophagic lysosomal reformation...
July 3, 2023: Nature Communications