Lysosomal Hydrolase Cathepsin D Non-proteolytically Modulates Dendritic Morphology in Drosophila

• 作者: Cunjin Wu Daxiao Cheng Huifang Lou Liya Zhu Qiang Ke Shumin Duan Ting Zhang Xiao-Dong Wang Xingyue Wang Yi-Jun Liu
• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2020,（10）
• 所属期刊栏目: Original Articles
• 页码范围: 1147-1157
• 页数: 11页
• 语种: 英文

摘要

The main lysosomal protease cathepsin D (cathD) is essential for maintaining tissue homeostasis via its degradative function,and its loss leads to ceroid accumulation in the mammalian nervous system,which results in progressive neurodegeneration.Increasing evidence implies non-proteolytic roles of cathD in regulating various biological processes such as apoptosis,cell proliferation,and migration.Along these lines,we here showed that cathD is required for modulating dendritic architecture in the nervous system independent of its traditional degradative function.Upon cathD depletion,class Ⅰ and class Ⅲ arborization (da) neurons in Drosophila larvae exhibited aberrant dendritic morphology,including overbranching,aberrant turning,and elongation defects.Reintroduction of wild-type cathD or its proteolyticallyinactive mutant dramatically abolished these morphological defects.Moreover,cathD knockdown also led to dendritic defects in the adult mushroom bodies,suggesting that cathD-mediated processes are required in both the peripheral and central nervous systems.Taken together,our results demonstrate a critical role of cathD in shaping dendritic architecture independent of its proteolytic function.