Abstract
Pruning of unspecific neurites is an important mechanism during neuronal morphogenesis. Drosophila sensory neurons prune their dendrites during metamorphosis. Pruning dendrites are severed in their proximal regions. Prior to severing, dendritic microtubules undergo local disassembly, and dendrites thin extensively through local endocytosis. Microtubule disassembly requires a katanin homologue, but the signals initiating microtubule breakdown are not known. Here, we show that the kinase PAR‐1 is required for pruning and dendritic microtubule breakdown. Our data show that neurons lacking PAR‐1 fail to break down dendritic microtubules, and PAR‐1 is required for an increase in neuronal microtubule dynamics at the onset of metamorphosis. Mammalian PAR‐1 is a known Tau kinase, and genetic interactions suggest that PAR‐1 promotes microtubule breakdown largely via inhibition of Tau also in Drosophila. Finally, PAR‐1 is also required for dendritic thinning, suggesting that microtubule breakdown might precede ensuing plasma membrane alterations. Our results shed light on the signaling cascades and epistatic relationships involved in neurite destabilization during dendrite pruning.
Synopsis

The developmental elimination of long stretches of neurite during neuronal morphogenesis—also known as pruning—involves the disassembly of microtubules in affected neurites. Using genetic and imaging analyses of dendrite pruning in Drosophila, we found that microtubule disruption is driven by the kinase PAR‐1, likely via an inhibitory effect on Tau.
Mutation or knockdown of PAR‐1 leads to dendrite pruning defects.
Loss of PAR‐1 prevents microtubule disruption during pruning.
PAR‐1 increases microtubule dynamics at the onset of pruning.
Genetic analysis suggests Tau is the relevant PAR‐1 target.
PAR‐1 is also required for subsequent membrane collapse.
The EMBO Journal (2017) 36: 1981–1991
- Received October 15, 2016.
- Revision received April 21, 2017.
- Accepted April 26, 2017.
- © 2017 The Authors
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