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Mucus secretion blocked at its source in the lungs

Higher than normal secretion of mucin, a molecular component of mucus, is a feature of many lung diseases. The development of a peptide that blocks mucin secretion in airway epithelial cells might lead to therapies.
  1. Irina Gitlin

    1. Irina Gitlin is at the Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94143, USA.

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  2. John V. Fahy

    1. John V. Fahy are at the Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94143, USA, and in the Division of Pulmonary and Critical Care Medicine, University of California, San Francisco.

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Excessive production and secretion of mucins (the gel-forming protein components of mucus) contribute to the formation of mucus that causes blockade of the airways in many lung conditions1. Mucins are produced by goblet cells (a type of epithelial cell that lines the airways) and by mucous cells in submucosal glands. They are packaged intracellularly in vesicles called secretory granules. Molecules that stimulate mucin secretion (termed mucin secretagogues), such as ATP, initiate a signalling cascade that results in calcium-ion-triggered fusion of the granule and cell membranes2. The proteins that mediate this fusion include SNARE proteins, which are located mainly in the cell membrane, and a calcium-sensor protein called synaptotagmin-2 that is present in the granule membrane. Writing in Nature, Lai et al.3 report that an engineered peptide disrupts the interaction of the SNARE complex with synaptotagmin-2, thereby blocking mucin secretion both in vitro and in vivo.

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Nature 603, 798-799 (2022)

doi: https://doi.org/10.1038/d41586-022-00700-8

References

  1. Ridley, C. & Thornton, D. J. Biochem. Soc. Trans. 46, 1099–1106 (2018).

    Article  PubMed  Google Scholar 

  2. Jaramillo, A. M., Azzegagh, Z., Tuvim, M. J. & Dickey, B. F. Ann. Am. Thorac. Soc. 15 (Suppl. 3), S164–S170 (2018).

    Article  PubMed  Google Scholar 

  3. Lai, Y. et al. Nature 603, 949–956 (2022).

    Article  Google Scholar 

  4. Boucher, R. C. N. Engl. J. Med. 380, 1941–1953 (2019).

    Article  PubMed  Google Scholar 

  5. Fahy, J. V. & Dickey, B. F. N. Engl. J. Med. 363, 2233–2247 (2010).

    Article  PubMed  Google Scholar 

  6. Yuan, S. et al. Sci. Transl. Med. 7, 276ra27 (2015).

    Article  PubMed  Google Scholar 

  7. Yang, C. & Montgomery, M. Cochrane Database Syst. Rev. 3, CD001127 (2021).

    PubMed  Google Scholar 

  8. Fahy, J. V., Kim, K. W., Liu, J. & Boushey, H. A. J. Allergy Clin. Immunol. 95, 843–852 (1995).

    Article  PubMed  Google Scholar 

  9. Bartoszewski, R., Matalon, S. & Collawn, J. F. Am. J. Physiol. Lung Cell. Mol. Physiol. 313, L859–L872 (2017).

    Article  PubMed  Google Scholar 

  10. Lillehoj, E. P., Kato, K., Lu, W. & Kim, K. W. Int. Rev. Cell Mol. Biol. 303, 139–202 (2013).

    Article  PubMed  Google Scholar 

  11. Castro, M. et al. N. Engl. J. Med. 378, 2486–2496 (2018).

    Article  PubMed  Google Scholar 

  12. Woodruff, P. G. et al. Am. J. Respir. Crit. Care Med. 181, 438–445 (2010).

    Article  PubMed  Google Scholar 

  13. Moiola, M., Memeo, M. G. & Quadrelli, P. Molecules 24, 3654 (2019).

    Article  Google Scholar 

  14. Verdine, G. L. & Hilinski, G. J. Methods Enzymol. 503, 3–33 (2012).

    Article  PubMed  Google Scholar 

Download references

Competing Interests

The authors are named inventors on patents for thiol saccharide-based mucolytic drugs, and they are both shareholders in a start-up biotechnology company (Aer Therapeutics) that seeks to advance novel mucolytic therapies to the clinic for treatment of lung disease.

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