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

PLoS Genet. 2020 Feb 14;16(2):e1008626. doi: 10.1371/journal.pgen.1008626. eCollection 2020 Feb.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Line
  • Dendrites / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development*
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental*
  • Gene Knockdown Techniques
  • I-kappa B Kinase / metabolism*
  • Intravital Microscopy
  • Microtubule-Associated Proteins / metabolism
  • Neuronal Plasticity / genetics*
  • Sensory Receptor Cells / cytology
  • Sensory Receptor Cells / physiology*
  • Signal Transduction / physiology
  • Time-Lapse Imaging
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*
  • rab11 GTP-Binding Proteins

Substances

  • Drosophila Proteins
  • I-kappa B Kinase
  • Microtubule-Associated Proteins
  • rab GTP-Binding Proteins
  • Spn-F protein, Drosophila
  • IKKepsilon protein, Drosophila
  • Rab11 protein, Drosophila
  • rab11 GTP-Binding Proteins