Mucus secretion blocked at its source in the lungs

Gitlin, Irina; Fahy, John V.

doi:10.1038/d41586-022-00700-8

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23 March 2022

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.

Irina Gitlin⁰ &
John V. Fahy¹

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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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

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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.