Nociceptor translational profiling reveals the RagA-mTORC1 network as a critical generator of neuropathic pain
Pradipta R Ray,
Jamie K. Moy,
Robert Y. North,
Patrick M. Dougherty,
Kevin R. Webster,
Zachary T Campbell,
Theodore J Price
Posted 02 Jun 2018
bioRxiv DOI: 10.1101/336784
Posted 02 Jun 2018
Pain sensing neurons, nociceptors, are key drivers of neuropathic pain. We used translating ribosome affinity purification (TRAP) to comprehensively characterize up- and down-regulated mRNA translation in Scn10a-positive nociceptors in chemotherapy-induced neuropathic pain. We provide evidence that an underlying mechanism driving these changes in gene expression is a sustained mTORC1 activation driven by MNK1-eIF4E signaling. RagA, a GTPase controlling mTORC1 activity, is identified as a novel target of MNK1-eIF4E signaling, demonstrating a new link between these distinct signaling pathways. Neuropathic pain and RagA translation are strongly attenuated by genetic ablation of eIF4E phosphorylation, MNK1 elimination or treatment with the MNK inhibitor eFT508. We reveal a novel translational circuit for the genesis of neuropathic pain with important implications for next generation neuropathic pain therapeutics.
- Downloaded 737 times
- Download rankings, all-time:
- Site-wide: 41,281
- In neuroscience: 5,594
- Year to date:
- Site-wide: 115,468
- Since beginning of last month:
- Site-wide: 85,099
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!