Lysosomes are involved in many cellular functions, and in turn lysosomal dysfunction underlies a variety of diseases, including cancer and neurodegenerative diseases. Lysosomes are distributed broadly in the cytoplasm and can move throughout the cell in kinesin- and dynein-dependent manners. Although many mechanisms of lysosomal transport have been reported, how lysosomal transport is regulated has yet to be fully elucidated. In this study we analyzed c-Jun NH2-terminal kinase-associated leucine zipper protein (JLP), an adaptor of kinesin and dynein motor proteins, and found that lysosomes were localized toward the cell periphery in JLP knockdown cells, leading to the impairment of autophagosome-lysosome fusion. Furthermore, we performed rescue experiments using wild-type JLP and its various deletion mutants. The results indicated that JLP may regulate lysosome localization and autophagy through interaction of JLP with kinesin-1 heavy chain, but not with dynactin p150Glued or lysosomal transmembrane protein 55b. Our findings provide new insights into the mechanisms of lysosomal trafficking regulation. This study contributes to the understanding of how lysosomes exert their multiple functions, potentially leading to the identification of molecular targets for diseases caused by lysosomal dysfunction.
Keywords: dynein; kinesin; lysosomal transport.