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Terminal Axon Branching Is Regulated by the LKB1-NUAK1 Kinase Pathway via Presynaptic Mitochondrial Capture
Open accessAbstract
SUMMARY The molecular mechanisms underlying the axon arborization of mammalian neurons are poorly understood but are critical for the establishment of functional neural circuits. We identified a pathway defined by two kinases, LKB1 and NUAK1, required for cortical axon branching in vivo. Conditional deletion of LKB1 after axon specification or knockdown of NUAK1 drastically reduced axon branching in vivo whereas their overexpression was sufficient to increase axon branching. The LKB1-NUAK1 pathway controls mitochondria immobilization in axons. Using manipulation of Syntaphilin, a protein necessary and sufficient to arrest mitochondrial transport specifically in the axon, we demonstrate that the LKB1-NUAK1 kinase pathway regulates axon branching by promoting mitochondria immobilization. Finally, we show that LKB1 and NUAK1 are necessary and sufficient to immobilize mitochondria specifically at nascent presynaptic sites. Our results unravel a link between presynaptic mitochondrial capture and axon branching.
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LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR‐1
Lizcano, J. M., Göransson, O., Toth, R., Deak, M., Morrice, N. A., Boudeau, J., Hawley, S. A., Udd, L., Mäkelä, T. P., Hardie, D. G., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600110 · Cited by 1,381
Zoghbi, H. Y., & Bear, M. F. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009886 · Cited by 797
Cited by
AMP-activated protein kinase mediates mitochondrial fission in response to energy stress
Toyama, E. Q., Herzig, S., Courchet, J., Lewis, T. L., Losón, O. C., Hellberg, K., Young, N. P., Chen, H., Polleux, F., Chan, D. C., et al. (2016) · Science · doi:10.1126/science.aab4138 · Cited by 1,085
Self-citationExcitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration
Verma, M., Lizama, B. N., & Chu, C. T. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-021-00278-7 · Cited by 451
A cannabinoid link between mitochondria and memory
Hebert-Chatelain, E., Desprez, T., Serrat, R., Bellocchio, L., Soria-Gomez, E., Busquets-Garcia, A., Pagano Zottola, A. C., Delamarre, A., Cannich, A., Vincent, P., et al. (2016) · Nature · doi:10.1038/nature20127 · Cited by 434
Picard, M., McManus, M. J., Gray, J. D., Nasca, C., Moffat, C., Kopinski, P. K., Seifert, E. L., McEwen, B. S., & Wallace, D. C. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515733112 · Cited by 293
Lewis, T. L., Kwon, S.-K., Lee, A., Shaw, R., & Polleux, F. (2018) · Nature Communications · doi:10.1038/s41467-018-07416-2 · Cited by 260
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Metadata
- Authors
- Courchet, J., Lewis, T. L., Lee, S., Courchet, V., Liou, D.-Y., Aizawa, S., & Polleux, F.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 153
- Issue
- 7
- Pages
- 1510-1525
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2044171033
- Cited by
- 349
- References
- 2
- FWCI
- 13.83
- Type
- journal article
- Language
- en
- Open access
- bronze
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