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Regulation of somatosensory mechanotransduction by Annexin A6

Ramin Raouf, Stéphane Lolignier, Jane E. Sexton, Queensta Millet, Sonia Santana-Varela, Anna Biller, Alice M. Fuller, Vanessa Pereira, Jyoti Choudhary, Mark Collins, Stephen E. Moss, Julie Tordo, Michael Linden, John N Wood
doi: https://doi.org/10.1101/155812
Ramin Raouf
1 Molecular Nociception Group, Wolfson Institute for Biomedical Research, UCL, Gower Street, London, WC1E 6BT, UK
2 current address: Wolfson Centre for Age-Related Diseases, King’s College London, London, SE1 1UL, UK
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Stéphane Lolignier
1 Molecular Nociception Group, Wolfson Institute for Biomedical Research, UCL, Gower Street, London, WC1E 6BT, UK
3 current address: NEURO-DOL, UMR1107 INSERM/Université Clermont Auvergne, 63000 Clermont-Ferrand, France
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Jane E. Sexton
1 Molecular Nociception Group, Wolfson Institute for Biomedical Research, UCL, Gower Street, London, WC1E 6BT, UK
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Queensta Millet
1 Molecular Nociception Group, Wolfson Institute for Biomedical Research, UCL, Gower Street, London, WC1E 6BT, UK
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Sonia Santana-Varela
1 Molecular Nociception Group, Wolfson Institute for Biomedical Research, UCL, Gower Street, London, WC1E 6BT, UK
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Anna Biller
1 Molecular Nociception Group, Wolfson Institute for Biomedical Research, UCL, Gower Street, London, WC1E 6BT, UK
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Alice M. Fuller
1 Molecular Nociception Group, Wolfson Institute for Biomedical Research, UCL, Gower Street, London, WC1E 6BT, UK
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Vanessa Pereira
1 Molecular Nociception Group, Wolfson Institute for Biomedical Research, UCL, Gower Street, London, WC1E 6BT, UK
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Jyoti Choudhary
4 Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
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Mark Collins
5 Department of Biomedical Science, The University of Sheffield, Western Bank, Sheffield S10 2TN UK
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Stephen E. Moss
6 Institute of Ophthalmology, UCL, 11-43 Bath Street, London, EC1V 9EL, UK
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Julie Tordo
7 Department of Infectious Diseases, King’s College London School of Medicine, London, SE1 9RT, UK
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Michael Linden
7 Department of Infectious Diseases, King’s College London School of Medicine, London, SE1 9RT, UK
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John N Wood
2 current address: Wolfson Centre for Age-Related Diseases, King’s College London, London, SE1 1UL, UK
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  • For correspondence: j.wood@ucl.ac.uk
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Abstract

Sensory neuron mechanically-activated slowly adapting currents have been linked to noxious mechanosensation. We identified a Conotoxin, Noxious Mechanosensation Blocker -1, that blocks such currents selectively and inhibits mechanical pain Using an active biotinylated form of the toxin we identified 67 binding proteins in sensory neurons and sensory neuron-derived cell lines using mass spectrometry. Annexin A6 was the most frequently identified binding protein. Annexin A6 knockout mice showed an enhanced sensitivity to mechanical stimuli. An increase in rapidly adapting currents was observed in sensory neurons alongside a decrease in slowly adapting currents. Conversely, overexpression of Annexin A6 in sensory neurons inhibited rapidly adapting currents and augmented slowly adapting currents. Furthermore, co-expression of Annexin A6 with Piezo2 led to an inhibition of Piezo-mediated rapidly adapting currents. AAV-mediated overexpression of Annexin A6 in sensory neurons attenuated mechanical pain in a mouse model of osteoarthritis. These data demonstrate a modulatory role for Annexin A6 in somatosensory mechanotransduction.

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Posted June 26, 2017.
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Regulation of somatosensory mechanotransduction by Annexin A6
Ramin Raouf, Stéphane Lolignier, Jane E. Sexton, Queensta Millet, Sonia Santana-Varela, Anna Biller, Alice M. Fuller, Vanessa Pereira, Jyoti Choudhary, Mark Collins, Stephen E. Moss, Julie Tordo, Michael Linden, John N Wood
bioRxiv 155812; doi: https://doi.org/10.1101/155812
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Regulation of somatosensory mechanotransduction by Annexin A6
Ramin Raouf, Stéphane Lolignier, Jane E. Sexton, Queensta Millet, Sonia Santana-Varela, Anna Biller, Alice M. Fuller, Vanessa Pereira, Jyoti Choudhary, Mark Collins, Stephen E. Moss, Julie Tordo, Michael Linden, John N Wood
bioRxiv 155812; doi: https://doi.org/10.1101/155812

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