Inhibition of Somatosensory Mechanotransduction by Annexin A6

Overview

Journal Sci Signal

Specialties Cell Biology
Physiology
Science

Date 2018 Jun 21

PMID 29921656

Citations 6

Authors

Ramin Raouf

Stephane Lolignier

Jane E Sexton

Queensta Millet

Sonia Santana-Varela

Anna Biller

Alice M Fuller

Vanessa Pereira

Jyoti S Choudhary

Mark O Collins

Stephen E Moss

Richard Lewis

Julie Tordo

Els Henckaerts

Michael Linden

John N Wood

Affiliations

Soon will be listed here.

Abstract

Mechanically activated, slowly adapting currents in sensory neurons have been linked to noxious mechanosensation. The conotoxin NMB-1 (noxious mechanosensation blocker-1) blocks such currents and inhibits mechanical pain. Using a biotinylated form of NMB-1 in mass spectrometry analysis, we identified 67 binding proteins in sensory neurons and a sensory neuron-derived cell line, of which the top candidate was annexin A6, a membrane-associated calcium-binding protein. Annexin A6-deficient mice showed increased sensitivity to mechanical stimuli. Sensory neurons from these mice showed increased activity of the cation channel Piezo2, which mediates a rapidly adapting mechano-gated current linked to proprioception and touch, and a decrease in mechanically activated, slowly adapting currents. Conversely, overexpression of annexin A6 in sensory neurons inhibited rapidly adapting currents that were partially mediated by Piezo2. Furthermore, overexpression of annexin A6 in sensory neurons attenuated mechanical pain in a mouse model of osteoarthritis, a disease in which mechanically evoked pain is particularly problematic. These data suggest that annexin A6 can be exploited to inhibit chronic mechanical pain.

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