title: S6 kinase inhibits intrinsic axon regeneration capacity via AMP kinase in Caenorhabditis elegans.
abstract: The ability of axons to regrow after injury is determined by the complex interplay of intrinsic growth programs and external cues. In Caenorhabditis elegans mechanosensory neuron, axons exhibit robust regenerative regrowth following laser axotomy. By surveying conserved metabolic signaling pathways, we have identified the ribosomal S6 kinase RSKS-1 as a new cell-autonomous inhibitor of axon regeneration. RSKS-1 is not required for axonal development but inhibits axon regrowth after injury in multiple neuron types. Loss of function in rsks-1 results in more rapid growth cone formation after injury and accelerates subsequent axon extension. The enhanced regrowth of rsks-1 mutants is partly dependent on the DLK-1 MAPK cascade. An essential output of RSKS-1 in axon regrowth is the metabolic sensor AMP kinase, AAK-2. We further show that the antidiabetic drug phenformin, which activates AMP kinase, can promote axon regrowth. Our data reveal a new function for an S6 kinase acting through an AMP kinase in regenerative growth of injured axons.
authors.affiliation: Division of Biological Sciences, Section of Neurobiology, and Howard Hughes Medical Institute, University of California San Diego, La Jolla, California 92093.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hubert
authors.forename: Zilu
authors.initials: Z
authors.lastname: Wu
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Chisholm
authors.forename: Yishi
authors.initials: Y
authors.lastname: Jin
mesh_terms: D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000201:enzymology*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology*; D019076:Transgenes / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D017346:Protein Serine-Threonine Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C571892:Rsks-1 protein, C elegans; C510541:AAK-2 protein, C elegans; D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase
keywords: AMP kinase; Caenorhabditis elegans; DLK kinase; laser axotomy; ribosomal S6 kinase