title: Terminal axon branching is regulated by the LKB1-NUAK1 kinase pathway via presynaptic mitochondrial capture.
abstract: 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.
authors.affiliation: Dorris Neuroscience Center and Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA 92037-1000, USA.
authors.forename: Julien
authors.initials: J
authors.lastname: Courchet
authors.forename: Tommy L
authors.initials: TL
authors.lastname: Lewis
authors.forename: Sohyon
authors.initials: S
authors.lastname: Lee
authors.forename: Virginie
authors.initials: V
authors.lastname: Courchet
authors.forename: Deng-Yuan
authors.initials: DY
authors.lastname: Liou
authors.forename: Shinichi
authors.initials: S
authors.lastname: Aizawa
authors.forename: Franck
authors.initials: F
authors.lastname: Polleux
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D005260:Female; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; C527531:Snph protein, mouse; D011494:Protein Kinases; C571903:NUAK1 protein, mouse; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases