Serglycin is essential for maturation of mast cell secretory granule.
To address the biological function of the scarcely studied intracellular proteoglycans, we targeted the gene for serglycin (SG), the only known committed intracellular proteoglycan. SG-/- mice developed normally and were fertile, but their mast cells (MCs) were severely affected. In peritoneum there was a complete absence of normal granulated MCs. Furthermore, peritoneal cells and ear tissue from SG-/- animals were devoid of the various MC-specific proteases. However, mRNA for the proteases was present in SG+/+, SG+/-, and SG-/- tissues, indicating that SG is essential for the storage, but not expression, of the MC proteases. Experiments, in which the differentiation of bone marrow stem cells into mature MCs was followed, showed that secretory granule maturation was compromised in SG-/- cells. Moreover, SG+/+ and SG+/- cells, but not SG-/- cells, synthesized proteoglycans of high anionic charge density. Taken together, we demonstrate a key role for SG proteoglycan in MC function.
Abrink
Magnus
M
Swedish University of Agricultural Sciences, Department of Molecular Biosciences, the Biomedical Centre, Box 575, 751 23 Uppsala, Sweden.
Grujic
Mirjana
M
Pejler
Gunnar
G
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D002478:Cells, Cultured; D020451:Contig Mapping; D003594:Cytoplasmic Granules / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D005091:Exons; D018390:Gene Targeting; D005838:Genotype; D006025:Glycosaminoglycans / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D010537:Peritoneum / Q000166:cytology; D010641:Phenotype; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022142:Secretory Vesicles / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D033921:Vesicular Transport Proteins
D006025:Glycosaminoglycans; D011509:Proteoglycans; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; C075430:serglycin; D004247:DNA; D019009:Proto-Oncogene Proteins c-kit; D010450:Endopeptidases; D012697:Serine Endopeptidases