A novel cysteine-rich adaptor protein is required for mucin packaging and secretory granule stability in vivo

• 成果类型: Article
• 署名作者: Zhang, Liping; Muirhead, Kayla J.; Syed, Zulfeqhar A.; Dimitriadis, Emilios K.; Hagen, Kelly G. Ten
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR); National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); National Institutes of Health (NIH) - USA; NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15429
• DOI: 10.1073/pnas.2314309121
• 发表日期: 2024-02-06
• 关键词: salivary-gland secretion; drosophila-melanogaster; glue proteins; mucus; release; packing; MODEL

摘要

Mucins are large, highly glycosylated extracellular matrix proteins that line and protect epithelia of the respiratory, digestive, and urogenital tracts. Previous work has shown that mucins form large, interconnected polymeric networks that mediate their biological functions once secreted. However, how these large matrix molecules are compacted and packaged into much smaller secretory granules within cells prior to secretion is largely unknown. Here, we demonstrate that a small cysteine-rich adaptor protein is essential for proper packaging of a secretory mucin in vivo. This adaptor acts via cysteine bonding between itself and the cysteine-rich domain of the mucin. Loss of this adaptor protein disrupts mucin packaging in secretory granules, alters the mobile fraction within granules, and results in granules that are larger, more circular, and more fragile. Understanding the factors and mechanisms by which mucins and other highly glycosylated matrix proteins are properly packaged and secreted may provide insight into diseases characterized by aberrant mucin secretion.