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Axotomy-induced HIF-serotonin signalling axis promotes axon regeneration in C. elegans

Tanimul Alam, Hiroki Maruyama, Chun Li, Strahil Iv. Pastuhov, Paola Nix, Michael Bastiani, Naoki Hisamoto () and Kunihiro Matsumoto ()
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Tanimul Alam: Graduate School of Science, Nagoya University, Chikusa-ku
Hiroki Maruyama: Graduate School of Science, Nagoya University, Chikusa-ku
Chun Li: Graduate School of Science, Nagoya University, Chikusa-ku
Strahil Iv. Pastuhov: Graduate School of Science, Nagoya University, Chikusa-ku
Paola Nix: University of Utah
Michael Bastiani: University of Utah
Naoki Hisamoto: Graduate School of Science, Nagoya University, Chikusa-ku
Kunihiro Matsumoto: Graduate School of Science, Nagoya University, Chikusa-ku

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract The molecular mechanisms underlying the ability of axons to regenerate after injury remain poorly understood. Here we show that in Caenorhabditis elegans, axotomy induces ectopic expression of serotonin (5-HT) in axotomized non-serotonergic neurons via HIF-1, a hypoxia-inducible transcription factor, and that 5-HT subsequently promotes axon regeneration by autocrine signalling through the SER-7 5-HT receptor. Furthermore, we identify the rhgf-1 and rga-5 genes, encoding homologues of RhoGEF and RhoGAP, respectively, as regulators of axon regeneration. We demonstrate that one pathway initiated by SER-7 acts upstream of the C. elegans RhoA homolog RHO-1 in neuron regeneration, which functions via G12α and RHGF-1. In this pathway, RHO-1 inhibits diacylglycerol kinase, resulting in an increase in diacylglycerol. SER-7 also promotes axon regeneration by activating the cyclic AMP (cAMP) signalling pathway. Thus, HIF-1-mediated activation of 5-HT signalling promotes axon regeneration by activating both the RhoA and cAMP pathways.

Date: 2016
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DOI: 10.1038/ncomms10388

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