SAD Kinases Sculpt Axonal Arbors of Sensory Neurons through Long- and Short-Term Responses to Neurotrophin Signals

Brendan N. Lilley, Y. Albert Pan, Joshua R. Sanes

Research output: Contribution to journalArticle

39 Scopus citations

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

Original languageEnglish (US)
Pages (from-to)39-53
Number of pages15
JournalNeuron
Volume79
Issue number1
DOIs
StatePublished - Jul 10 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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