Lysosomal Cathepsin D Regulates The Dendritic Development In Drosophila Sensory Neuron

Cathepsin D is a critical protease in the endosome/lysosome(LE/LY)system.Dependent on the acidic environment in LE/LY vesicles,cathD regulates various physiological and pathological processes based on its proteolytic activity.Previous studies have shown that the protein expression level of cathD is down-regulated during neurodegenerative diseases.Frequently these diseases are accompanied with morphological changes such as dendrite withering,spine loss,and decrease of dendritic complexity.There results suggest that cathD may regulate dendritic development with unknown mechanism.To address this question,we established cath D knockout Drosophila strain and observed and monitored the dendritic development in class IV dendritic arborization neurons in Drosophila melanogaster larvae.Comparison with control neurons,we found that cathD depletion shortened neuron dendrites and decreased dendritic branches.Expression of wild-type cathD completely reversed these morphologic defects,whereas expression of proteolytic mutant cathD showed no effects.These results suggest a regulatory role of cathD regulating dendritic length and branch number dependent on its proteolytic activity.Furthermore,we also found that cathD depletion led to abnormal proliferation of dendritic terminals,which phenotype could be reversed by expression of wild-type cathD or its proteolytic inactive mutant.These results suggest that cathD tunes the terminal development in dendrites independent on its proteolytic activity.Taken together,cathD modulates neuron dendritic length and branch depends on its proteolytic activity,and dendritic terminals independent on proteolysis function.