Poster Sessions

CB -39

Qian Cai

Q. Cai, L. Lu, J. H. Tian, Z. H. Sheng

Essential Role of Snapin in Coordinating Late Endocytic Trafficking and Autophagy-Lysosomal Function

Lysosomes are dynamic organelles that receive and degrade macromolecules and organelles from secretory, endocytic, and autophagic pathways during cellular homeostasis in health and disease. Although some features of late endocytic trafficking have been described, regulation of this process remains to be elucidated. Here, we report an essential role for Snapin in tightly coordinating late endocytic trafficking and autophagy-lysosomal funciton. Deletion of snapin results in abnormal accumulation of autolysosomes and late endosomes in neurons and fibroblasts; impaired degradation of internalized EGF and BSA-gold; retention of Dextran in late endosomes rather than delivery to lysosomes; and reduced maturation of the lysosomal enzyme cathepsin D. The phenotypes can be rescued by transiently reintroducing snapin into mutant cells. Furthermore, time-lapse imaging demonstrates that elevated Snapin expression accelerates late endosome-lysosome trafficking. Thus, our studies indicate that Snapin facilitates the late endocytic pathway, thereby highlighting a mechanistic insight into regulation of autophagy-lysosomal function.