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 language | English (US) |
|---|---|
| Pages (from-to) | 39-53 |
| Number of pages | 15 |
| Journal | Neuron |
| Volume | 79 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 10 2013 |
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ASJC Scopus subject areas
- Neuroscience(all)
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SAD Kinases Sculpt Axonal Arbors of Sensory Neurons through Long- and Short-Term Responses to Neurotrophin Signals. / Lilley, Brendan N.; Pan, Y. Albert; Sanes, Joshua R.
In: Neuron, Vol. 79, No. 1, 10.07.2013, p. 39-53.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - SAD Kinases Sculpt Axonal Arbors of Sensory Neurons through Long- and Short-Term Responses to Neurotrophin Signals
AU - Lilley, Brendan N.
AU - Pan, Y. Albert
AU - Sanes, Joshua R.
PY - 2013/7/10
Y1 - 2013/7/10
N2 - 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
AB - 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
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UR - http://www.scopus.com/inward/citedby.url?scp=84880043350&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2013.05.017
DO - 10.1016/j.neuron.2013.05.017
M3 - Article
C2 - 23790753
AN - SCOPUS:84880043350
VL - 79
SP - 39
EP - 53
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 1
ER -