Lysosomal Hydrolase Cathepsin D Non-proteolytically Modulates Dendritic Morphology in Drosophila
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ORIGINAL ARTICLE
Lysosomal Hydrolase Cathepsin D Non-proteolytically Modulates Dendritic Morphology in Drosophila Ting Zhang1 • Daxiao Cheng1 • Cunjin Wu1 • Xingyue Wang1 • Qiang Ke2,3 • Huifang Lou1 Liya Zhu1 • Xiao-Dong Wang1,4 • Shumin Duan1,5 • Yi-Jun Liu1
•
Received: 14 November 2019 / Accepted: 19 December 2019 Ó The Author(s) 2020
Abstract 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.
Ting Zhang, Daxiao Cheng and Cunjin Wu have contributed equally to this work.
Keywords Cathepsin D Dendritic arborization Sensory neuron Mushroom body Actin Drosophila
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12264-020-00479-6) contains supplementary material, which is available to authorized users. & Shumin Duan [email protected] & Yi-Jun Liu [email protected] 1
Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, China
2
Department of Diagnostics, Hangzhou Normal University Medical School, Hangzhou 311121, China
3
Department of Laboratory Medicine, Hangzhou Normal University Affiliated Hospital, Hangzhou 310015, China
4
Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
5
Mental Health Center, Zhejiang University School of Medicine, Hangzhou 310058, China
Introduction Endosome/lysosomes are key organelles in eukaryotic cells, containing a wide variety of hydrolases responsible for the turnover of macromolecules. Among the lysosomal hydrolases, cathepsin D (cathD) is the main acidic hydrolase responsible for nonspecific protein degradation [1]. Although other lysosomal hydrolases may replace cathD to mediate proteolysis, cath
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