Yang, Nicole J., Isensee, Joerg, Neel, Dylan, V, Quadros, Andreza U., Zhang, Han-Xiong Bear, Lauzadis, Justas, Liu, Sai Man ORCID: 0000-0001-6359-0229, Shiers, Stephanie, Belu, Andreea, Palan, Shilpa, Marlin, Sandra, Maignel, Jacquie, Kennedy-Curran, Angela, Tong, Victoria S., Moayeri, Mahtab, Roederer, Pascal, Nitzsche, Anja, Lu, Mike, Pentelute, Bradley L., Bruestle, Oliver, Tripathi, Vineeta, Foster, Keith A., Price, Theodore J., Collier, R. John, Leppla, Stephen H., Puopolo, Michelino, Bean, Bruce P., Cunha, Thiago M., Hucho, Tim and Chiu, Isaac M. . Anthrax toxins regulate pain signaling and can deliver molecular cargoes into ANTXR2(+) DRG sensory neurons. Nat. Neurosci.. BERLIN: NATURE PORTFOLIO. ISSN 1546-1726

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Abstract

Discovering that nociceptive sensory neurons express the receptor for anthrax toxin, Yang et al. show that anthrax toxin can induce potent analgesia in mice and facilitate the delivery of potentially analgesic cargo proteins into nociceptive neurons. 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 Na(v)1.8(+) 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Yang, Nicole J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isensee, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neel, Dylan, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Quadros, Andreza U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, Han-Xiong BearUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lauzadis, JustasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, Sai ManUNSPECIFIEDorcid.org/0000-0001-6359-0229UNSPECIFIED
Shiers, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belu, AndreeaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palan, ShilpaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marlin, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maignel, JacquieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kennedy-Curran, AngelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tong, Victoria S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moayeri, MahtabUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roederer, PascalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nitzsche, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lu, MikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pentelute, Bradley L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruestle, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tripathi, VineetaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foster, Keith A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Price, Theodore J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Collier, R. JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leppla, Stephen H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Puopolo, MichelinoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bean, Bruce P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cunha, Thiago M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hucho, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chiu, Isaac M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-602871
DOI: 10.1038/s41593-021-00973-8
Journal or Publication Title: Nat. Neurosci.
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 1546-1726
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CAPILLARY MORPHOGENESIS PROTEIN-2; I PROJECTION NEURONS; SPINAL DORSAL-HORN; EDEMA TOXIN; CYCLIC-AMP; RECEPTOR; BINDING; TISSUE; CELL; KINASEMultiple languages
NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60287

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