title: A role for serglycin proteoglycan in granular retention and processing of mast cell secretory granule components.
abstract: In the absence of serglycin proteoglycans, connective tissue-type mast cells fail to assemble mature metachromatic secretory granules, and this is accompanied by a markedly reduced ability to store neutral proteases. However, the mechanisms behind these phenomena are not known. In this study, we addressed these issues by studying the functionality and morphology of secretory granules as well as the fate of the secretory granule proteases in bone marrow-derived mast cells from serglycin(+/+) and serglycin(-/-) mice. We show that functional secretory vesicles are formed in both the presence and absence of serglycin, but that dense core formation is defective in serglycin(-/-) mast cell granules. The low levels of mast cell proteases present in serglycin(-/-) cells had a granular location, as judged by immunohistochemistry, and were released following exposure to calcium ionophore, indicating that they were correctly targeted into secretory granules even in the absence of serglycin. In the absence of serglycin, the fates of the serglycin-dependent proteases differed, including preferential degradation, exocytosis or defective intracellular processing. In contrast, beta-hexosaminidase storage and release was not dependent on serglycin. Together, these findings indicate that the reduced amounts of neutral proteases in the absence of serglycin is not caused by missorting into the constitutive pathway of secretion, but rather that serglycin may be involved in the retention of the proteases after their entry into secretory vesicles.
authors.affiliation: Swedish University of Agricultural Sciences, Department of Molecular Biosciences, The Biomedical Center, 751-23 Uppsala, Sweden.
authors.forename: Frida
authors.initials: F
authors.lastname: Henningsson
authors.forename: Sonja
authors.initials: S
authors.lastname: Hergeth
authors.forename: Robert
authors.initials: R
authors.lastname: Cortelius
authors.forename: Magnus
authors.initials: M
authors.lastname: Abrink
authors.forename: Gunnar
authors.initials: G
authors.lastname: Pejler
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D005089:Exocytosis; D007476:Ionophores / Q000494:pharmacology; D008407:Mast Cells / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology*; D022142:Secretory Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000502:physiology*; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D007476:Ionophores; D011509:Proteoglycans; D033921:Vesicular Transport Proteins; C075430:serglycin; D000001:Calcimycin; D001619:beta-N-Acetylhexosaminidases