PT  - JOURNAL ARTICLE
AU  - Thomas Hubert
AU  - Zilu Wu
AU  - Andrew D. Chisholm
AU  - Yishi Jin
TI  - S6 Kinase Inhibits Intrinsic Axon Regeneration Capacity via AMP Kinase in <em>Caenorhabditis elegans</em>
AID  - 10.1523/JNEUROSCI.2886-13.2014
DP  - 2014 Jan 15
TA  - The Journal of Neuroscience
PG  - 758--763
VI  - 34
IP  - 3
4099  - http://www.jneurosci.org/content/34/3/758.short
4100  - http://www.jneurosci.org/content/34/3/758.full
SO  - J. Neurosci.2014 Jan 15; 34
AB  - 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.