| Literature DB >> 34931070 |
Nicole J Yang1, Jörg Isensee2, Dylan V Neel1, Andreza U Quadros3, Han-Xiong Bear Zhang4, Justas Lauzadis5, Sai Man Liu6, Stephanie Shiers7, Andreea Belu2, Shilpa Palan6, Sandra Marlin6, Jacquie Maignel8, Angela Kennedy-Curran1, Victoria S Tong1, Mahtab Moayeri9, Pascal Röderer10,11, Anja Nitzsche10,11, Mike Lu12, Bradley L Pentelute12,13,14,15, Oliver Brüstle10, Vineeta Tripathi6, Keith A Foster6, Theodore J Price7, R John Collier16, Stephen H Leppla9, Michelino Puopolo5, Bruce P Bean4, Thiago M Cunha3, Tim Hucho2, Isaac M Chiu17.
Abstract
Bacterial products can act on neurons to alter signaling and function. In the present study, we found that dorsal root ganglion (DRG) sensory neurons are enriched for ANTXR2, the high-affinity receptor for anthrax toxins. Anthrax toxins are composed of protective antigen (PA), which binds to ANTXR2, and the protein cargoes edema factor (EF) and lethal factor (LF). Intrathecal administration of edema toxin (ET (PA + EF)) targeted DRG neurons and induced analgesia in mice. ET inhibited mechanical and thermal sensation, and pain caused by formalin, carrageenan or nerve injury. Analgesia depended on ANTXR2 expressed by Nav1.8+ or Advillin+ neurons. ET modulated protein kinase A signaling in mouse sensory and human induced pluripotent stem cell-derived sensory neurons, and attenuated spinal cord neurotransmission. We further engineered anthrax toxins to introduce exogenous protein cargoes, including botulinum toxin, into DRG neurons to silence pain. Our study highlights interactions between a bacterial toxin and nociceptors, which may lead to the development of new pain therapeutics.Entities:
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Year: 2021 PMID： 34931070 PMCID： PMC9388775 DOI： 10.1038/s41593-021-00973-8
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 28.771