SAD kinases sculpt axonal arbors of sensory neurons through long- and short-term responses to neurotrophin signals

Neuron. 2013 Jul 10;79(1):39-53. doi: 10.1016/j.neuron.2013.05.017. Epub 2013 Jun 20.

Abstract

Extrinsic cues activate intrinsic signaling mechanisms to pattern neuronal shape and connectivity. We showed previously that three cytoplasmic Ser/Thr kinases, LKB1, SAD-A, and SAD-B, control early axon-dendrite polarization in forebrain neurons. Here, we assess their role in other neuronal types. We found that all three kinases are dispensable for axon formation outside of the cortex but that SAD kinases are required for formation of central axonal arbors by subsets of sensory neurons. The requirement for SAD kinases is most prominent in NT-3 dependent neurons. SAD kinases transduce NT-3 signals in two ways through distinct pathways. First, sustained NT-3/TrkC signaling increases SAD protein levels. Second, short-duration NT-3/TrkC signals transiently activate SADs by inducing dephosphorylation of C-terminal domains, thereby allowing activating phosphorylation of the kinase domain. We propose that SAD kinases integrate long- and short-duration signals from extrinsic cues to sculpt axon arbors within the CNS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Cell Polarity / physiology
  • Cerebral Cortex / metabolism
  • HeLa Cells
  • Humans
  • Mice
  • Neurotrophin 3 / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Receptor, trkC / metabolism
  • Sensory Receptor Cells / metabolism*
  • Signal Transduction / physiology*

Substances

  • Neurotrophin 3
  • Stk11 protein, mouse
  • Receptor, trkC
  • Brsk1 protein, mouse
  • Brsk2 protein, mouse
  • Protein-Serine-Threonine Kinases