title: Annexin A2 regulates TRPA1-dependent nociception.
abstract: The transient receptor potential A1 (TRPA1) channel is essential for vertebrate pain. Even though TRPA1 activation by ligands has been studied extensively, the molecular machinery regulating TRPA1 is only poorly understood. Using an unbiased proteomics-based approach we uncovered the physical association of Annexin A2 (AnxA2) with native TRPA1 in mouse sensory neurons. AnxA2 is enriched in a subpopulation of sensory neurons and coexpressed with TRPA1. Furthermore, we observe an increase of TRPA1 membrane levels in cultured sensory neurons from AnxA2-deficient mice. This is reflected by our calcium imaging experiments revealing higher responsiveness upon TRPA1 activation in AnxA2-deficient neurons. In vivo these findings are associated with enhanced nocifensive behaviors specifically in TRPA1-dependent paradigms of acute and inflammatory pain, while heat and mechanical sensitivity as well as TRPV1-mediated pain are preserved in AnxA2-deficient mice. Our results support a model whereby AnxA2 limits the availability of TRPA1 channels to regulate nociceptive signaling in vertebrates.
authors.affiliation: Somatosensory Signalling Group and.
authors.forename: Luca
authors.identifier: http://orcid.org/0000-0003-1418-0279
authors.initials: L
authors.lastname: Avenali
authors.affiliation: Somatosensory Signalling Group and.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Narayanan
authors.affiliation: Somatosensory Signalling Group and.
authors.forename: Tom
authors.initials: T
authors.lastname: Rouwette
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, D-37075 Goettingen, Germany.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cervellini
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, D-37075 Goettingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Sereda
authors.affiliation: Somatosensory Signalling Group and gomezvarela@em.mpg.de mschmidt@em.mpg.de.
authors.forename: David
authors.initials: D
authors.lastname: Gomez-Varela
authors.affiliation: Somatosensory Signalling Group and gomezvarela@em.mpg.de mschmidt@em.mpg.de.
authors.forename: Manuela
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology; D015220:Calcium Channels / Q000378:metabolism*; D057809:HEK293 Cells; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D059225:Nociception / Q000502:physiology*; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D010147:Pain Measurement; D010812:Physical Stimulation; D051381:Rats; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
chemical_list: D017306:Annexin A2; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels
keywords: TRPA1 channels; membrane abundance; nociception; protein–protein interaction