Rab11 activation by Ik2 kinase is required for dendrite pruning in Drosophila sensory neurons.

Tzu Lin,Hao-Hsiang Kao,Hsiu-Hsiang Lee,Yu-Ching Liao,Che-Hsuan Chou,Chih-Yu Chou,Bingwei Lu

doi:10.1371/journal.pgen.1008626

Abstract

Neuronal pruning is a commonly observed phenomenon for the developing nervous systems to ensure precise wiring of neural circuits. The function of Ik2 kinase and its downstream mediator, Spindle-F (Spn-F), are essential for dendrite pruning of Drosophila sensory neurons during development. However, little is known about how Ik2/Spn-F signaling is transduced in neurons and ultimately results in dendrite pruning. Our genetic analyses and rescue experiments demonstrated that the small GTPase Rab11, especially the active GTP-bound form, is required for dendrite pruning. We also found that Rab11 shows genetic interactions with spn-F and ik2 on pruning. Live imaging of single neurons and antibody staining reveal normal Ik2 kinase activation in Rab11 mutant neurons, suggesting that Rab11 could have a functional connection downstream of and/or parallel to the Ik2 kinase signaling. Moreover, we provide biochemical evidence that both the Ik2 kinase activity and the formation of Ik2/Spn-F/Rab11 complexes are central to promote Rab11 activation in cells. Together, our studies reveal that a critical role of Ik2/Spn-F signaling in neuronal pruning is to promote Rab11 activation, which is crucial for dendrite pruning in neurons.

Highlights

During the early development of the nervous systems, neurons often extend exuberant branches and make excessive connections in the vicinity of their final targets
Drosophila sensory neurons that undergo dendrite pruning provide us an opportunity to study the regulatory mechanism of neuronal pruning
The results from our studies reveal that a critical role of Ik2/Spn-F signaling in neuronal pruning is to promote Rab11 activation, which is crucial for dendrite pruning in C4da neurons

Summary

Introduction

During the early development of the nervous systems, neurons often extend exuberant branches and make excessive connections in the vicinity of their final targets. To ensure the precise neuronal wiring, further remodeling is required to refine the connections of the nervous systems at later developmental stages. One of the remodeling mechanisms, is a tightly controlled process to eliminate excessive branches and improper connections without causing any cell death. It has been shown that disrupting developmental pruning in neurons could reduce olfactory plasticity in C. elegans [3]. Blocking pruning in Drosophila brain mushroom body (MB) γ neurons has been shown to display ectopic connections affecting the olfactory circuits [4], and abolish short-term courtship memory in adult flies [5]. Any misregulation of pruning activity could severely affect the functions of nervous systems in animals

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