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Research article - Peer-reviewed, 2006

A role for serglycin proteoglycan in granular retention and processing of mast cell secretory granule components

Henningsson F, Hergeth S, Cortelius R, Abrink M, Pejler G

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

Published in

FEBS Journal
2006, Volume: 273, number: 21, pages: 4901-4912
Publisher: BLACKWELL PUBLISHING

      SLU Authors

    • Pejler, Gunnar

      • Department of Molecular Biosciences, Swedish University of Agricultural Sciences
    • UKÄ Subject classification

      Veterinary Science
      Animal and Dairy Science

      Publication identifier

      DOI: https://doi.org/10.1111/j.1742-4658.2006.05489.x

      Permanent link to this page (URI)

      https://res.slu.se/id/publ/10687