Cell
Volume 153, Issue 7, 20 June 2013, Pages 1510-1525
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Article
Terminal Axon Branching Is Regulated by the LKB1-NUAK1 Kinase Pathway via Presynaptic Mitochondrial Capture

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Highlights

  • Terminal axonal branching depends on postmitotic activity of LKB1 and NUAK1 kinases

  • LKB1-NUAK1 activity promotes axon branching through mitochondrial immobilization

  • Immobilization of mitochondria along the axon is required for branching

  • LKB1-NUAK1 promotes mitochondrial capture at nascent presynaptic boutons

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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These authors contributed equally to this work