biostudies-literatureSyed ZAHHS | NIH | National Institute of Dental and Craniofacial Research (NIDCR)HHS | NIH | National Institute of Dental and Craniofacial Researche2209750119https://www.ebi.ac.uk/biostudies/studies/S-EPMC9618048biostudies-literatureUnknown119(43)Mucins are large, highly glycosylated transmembrane and secreted proteins that line and protect epithelial surfaces. However, the details of mucin biosynthesis and packaging in vivo are largely unknown. Here, we demonstrate that multiple distinct mucins undergo intragranular restructuring during secretory granule maturation in vivo, forming unique structures that are spatially segregated within the same granule. We further identify temporally-regulated genes that influence mucin restructuring, including those controlling pH (<i>Vha16-1</i>), Ca²⁺ ions (<i>fwe</i>) and Cl^- ions (<i>Clic</i> and <i>ClC-c</i>). Finally, we show that altered mucin glycosylation influences the dimensions of these structures, thereby affecting secretory granule morphology. This study elucidProceedings of the National Academy of Sciences of the United States of AmericaRegulated Restructuring of Mucins During Secretory Granule Maturation In Vivo.PMC9618048Z01-DE-000713ZIC DE000750-01Tran DTZhang LBleck CKESyed ZATen Hagen KGfalseRegulated Restructuring of Mucins During Secretory Granule Maturation In Vivo.Mucins are large, highly glycosylated transmembrane and secreted proteins that line and protect epithelial surfaces. However, the details of mucin biosynthesis and packaging in vivo are largely unknown. Here, we demonstrate that multiple distinct mucins undergo intragranular restructuring during secretory granule maturation in vivo, forming unique structures that are spatially segregated within the same granule. We further identify temporally-regulated genes that influence mucin restructuring, including those controlling pH (<i>Vha16-1</i>), Ca²⁺ ions (<i>fwe</i>) and Cl^- ions (<i>Clic</i> and <i>ClC-c</i>). Finally, we show that altered mucin glycosylation influences the dimensions of these structures, thereby affecting secretory granule morphology. This study elucid2022-01-01T00:00:00Z2022 Oct2026-05-27T21:06:20.548Z2025-04-04T07:11:10.553ZS-EPMC96180483625201710.1073/pnas.2209750119