Abstract
Rationale: Finely tuned production and secretion of the polymeric mucins MUC5AC and MUCB are required for lung health, but knowledge of many details between their translation and their packaging into secretory granules is lacking. Objective: To analyze the structure and function of the Golgi apparatus, a key site of mucin glycosylation, folding, polymerization and packaging, in airway epithelial secretory cells. Methods: Lung tissue was obtained from mice stimulated or not with IL-13 to upregulate mucin production, and from normal human lungs. Golgi elements in mouse and human tissue were imaged by high-resolution immunofluorescence microscopy and electron microscopy. Tissue from mice with deletion of both polymeric mucins was also examined. Measurements and Main Results: By immunofluorescence microscopy, both mouse and human airway secretory cells contained ∼100 dispersed puncta labeled by markers of medial and trans Golgi cisternae and the trans-Golgi network (TGN), but only a few perinuclear puncta were labeled by markers of cis-Golgi cisternae. By electron microscopy, secretory cells contained both a perinuclear Golgi ribbon and numerous dispersed Golgi stacks, termed satellites. In mucous metaplastic cells, satellites were concentrated among immature mucin granules. Increasing mucin production by cytokine stimulation did not increase the number of TGN puncta, nor did preventing polymeric mucin production by gene deletion reduce TGN puncta. Conclusions: Mucin-producing airway secretory cells express an unusual Golgi structure consisting of a conventional perinuclear ribbon as well as dispersed satellites. While the Golgi satellites are likely an adaptation for mucin production and packaging, their presence is specified developmentally, independent of mucin production.
All Related Versions
Funding Information
  • National Institutes of Health (K99 HL165072)
  • National Institutes of Health (R01 HL138510)
  • National Institutes of Health (R01 HL157100)
  • National Institutes of Health (R01 HL080396)
  • National Institutes of Health (R01 HL130938)
  • National Institutes of Health (R01 HL179623)
  • National Institutes of Health (P01 HL162607)
  • National Institutes of Health (P30 EY007551)
  • National Institutes of Health (R01 HL129795)
  • National Institutes of Health (R01 HL080396)
  • Cystic Fibrosis Foundation (JARAMI20F0)
  • Cystic Fibrosis Foundation (DICKEY18G0)
  • Cystic Fibrosis Foundation (DICKEY19P0)
  • Cystic Fibrosis Foundation (DICKEY24P0)
  • U.S. Department of Veterans Affairs (IK2BX006462)
  • U.S. Department of Veterans Affairs (I01BX005343)
  • Vetenskapsrådet (2023–02474)
  • Knut och Alice Wallenbergs Stiftelse (2017-0028)
  • Swedish Cystic Fibrosis Foundation

This publication has 51 references indexed in Scilit: