SAD Kinases Sculpt Axonal Arbors of Sensory Neurons through Long- and Short-Term Responses to Neurotrophin Signals
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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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Several genes were assigned to clusters enriched for gene sets consistent with their known functions, including KDM1B, BRSK2, and ITSN1, consistent with published functional evidence.
“Several genes were assigned to clusters that showed enrichment for gene sets consistent with their known functions, including KDM1B,41 BRSK2,42 and ITSN143 consistent with published functional evidence”
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- Authors
- Lilley, B. N., Pan, Y. A., & Sanes, J. R.
- Affiliations
- Harvard University (US)
- Corresponding author
- Sanes, Joshua R.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 79
- Issue
- 1
- Pages
- 39-53
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3725037
- OpenAlex
- W2071055050
- Cited by
- 63
- References
- 69
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 8 · 2019: 3 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 5
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Damon Runyon Cancer Research Foundation
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R21NS076880, R37NS019195, R01NS029169)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- LKB1, sensory neurons, neurotrophin signaling, neurotrophin-3, TrkC, kinase dephosphorylation, kinase activation, central nervous system neurons
- MeSH terms
- Animals, Axons, Cerebral Cortex, HeLa Cells, Humans, Sensory Receptor Cells, Signal Transduction, Cell Polarity, Protein Serine-Threonine Kinases, Receptor, trkC, Neurotrophin 3, Mice, AMP-Activated Protein Kinases
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