Affiliation:
1. 1 Research Link, National University of Singapore 1 Temasek Life Sciences Laboratory , , Singapore 117604
2. National University of Singapore 2 Department of Biological Sciences , , Singapore 117543
Abstract
ABSTRACT
The evolutionarily conserved Glycogen Synthase Kinase 3β (GSK3β), a negative regulator of microtubules, is crucial for neuronal polarization, growth and migration during animal development. However, it remains unknown whether GSK3β regulates neuronal pruning, which is a regressive process. Here, we report that the Drosophila GSK3β homologue Shaggy (Sgg) is cell-autonomously required for dendrite pruning of ddaC sensory neurons during metamorphosis. Sgg is necessary and sufficient to promote microtubule depolymerization, turnover and disassembly in the dendrites. Although Sgg is not required for the minus-end-out microtubule orientation in dendrites, hyperactivated Sgg can disturb the dendritic microtubule orientation. Moreover, our pharmacological and genetic data suggest that Sgg is required to promote dendrite pruning at least partly via microtubule disassembly. We show that Sgg and Par-1 kinases act synergistically to promote microtubule disassembly and dendrite pruning. Thus, Sgg and Par-1 might converge on and phosphorylate a common downstream microtubule-associated protein(s) to disassemble microtubules and thereby facilitate dendrite pruning.
Funder
Temasek Life Sciences Laboratory
National Research Foundation Singapore
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology