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.
N1 - Funding Information:
We thank Marian Carlson, Susan Dymecki, Tom Jessell, Louis Reichardt, Michael Schneider, William Sellers, Li-Huei Tsai, Sander van den Heuvel, and Hans Widlund for mouse strains, antibodies, and plasmids used in this study; Debbie Pelusi for excellent technical assistance; Arjun Krishnaswamy and members of the Sanes lab for helpful suggestions. This work was supported by grants from the NIH (R01 NS029169 and R21 NS076880). B.N.L. was supported by a fellowship from the Damon Runyon Cancer Research Foundation (DRG-1914-06).
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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U2 - 10.1016/j.neuron.2013.05.017
DO - 10.1016/j.neuron.2013.05.017
M3 - Article
C2 - 23790753
AN - SCOPUS:84880043350
SN - 0896-6273
VL - 79
SP - 39
EP - 53
JO - Neuron
JF - Neuron
IS - 1
ER -