Abstract

Mast cell granule maturation and storage of granule components has previously been shown to be critically dependent oil serglycin (SG), a proteoglycan abundantly stored in mast cell secretory granules. The N-terminal portion of serglycin contains a conserved disulfide motif that is similar to motifs found in secretory granule compounds of neuroendocrine cells. Interference with such motifs of neuroendocrine cells with dithiothreitol (DTT) has previously been shown to cause cellular missorting. To investigate the implication for serglycin, serglycin(+/+) and serglycin(-/-) bone marrow derived mast cells (BMMCs) were treated with DTT followed by assessment of proteoglycan synthesis and secretory granule integrity. Treatment of serglycin(+/+) BMMCs with DTT almost completely abolished biosynthetic incorporation of (35)S-sulfate into proteoglycans, caused a dramatic reduction of granular staining with May Grunwald/Giemsa as well as disruption of granule dense core formation as shown by transmission electron microscopy. In addition, the storage of carboxypeptidase A, a major secretory granule compound, Was markedly reduced following DTT treatment. In contrast, none of these effects were seen after treatment of SG(-/-) BMMCs with DTT, indicating that they were serglycin-specific. Notably, D-TT treated serglycin(+/+) 4 BMMCs showed similar morphology as did the serglycin(+/+) BMMCs. DTT treatment affected neither the viability of the BMMCs nor the mRNA levels for serglycin or carboxypeptidase A. Together, these data indicate that DTT Causes dramatic, serglycin-specific effects on mast cell granule. These findings are thus in accordance with a role for the N-terminal disulfide motif in serglycin for regulation of mast cell secretory granule integrity. (C) 2008 Elsevier Ltd. All rights reserved.

Keywords

Serglycin; Proteoglycans; Mast cells; Intracellular sorting; Secretory granule

Published in

Molecular Immunology
2009, Volume: 46, number: 3, pages: 422-428
Publisher: PERGAMON-ELSEVIER SCIENCE LTD

SLU Authors

• Braga, Tiago

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

• Pejler, Gunnar

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Veterinary Science
Animal and Dairy Science


Publication identifier

DOI: https://doi.org/10.1016/j.molimm.2008.10.019

Permanent link to this page (URI)

https://res.slu.se/id/publ/61650