Serglycin Is Essential for Maturation of Mast Cell Secretory Granule

Abstract

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.

Heparan Sulfate Proteoglycans

“…Serglycin Null allele: viable; secretory granule defects in mast cells (Abrink et al 2004); dense core formation is defective in mast cell granules (Henningsson et al 2006); defective secretory granule maturation and granzyme B storage in cytotoxic T cells (Grujic et al 2005); no effect on macrophages (Zernichow et al 2006); platelets and megakaryocytes contain unusual scroll-like membranous inclusions (Woulfe et al 2008); enlargement of multiple lymphoid organs, decrease in the proportion of CD4 þ cells, more pronounced airway inflammatory response in older mice (Wernersson et al 2009); increased virulence of Klebsiella pneumoniae (Niemann et al 2007); defective regulation of antiviral CD8 þ T-cell responses (Grujic et al 2008). Agrn Agrin Null allele: embryonic lethal; reduced number, size, and density of postsynaptic acetylcholine receptor aggregates in muscles; abnormal intramuscular nerve branching and presynaptic differentiation (Gautam et al 1996(Gautam et al ,1999; smaller brains (Serpinskaya et al 1999); abnormal development of interneuronal synapses (Gingras et al 2007); increased resistance to excitotoxic injury (Hilgenberg et al 2002); reduced number of cortical presynaptic and postsynaptic specializations (Ksiazek et al 2007).…”

Serglycin inhibits the classical and lectin pathways of complement via its glycosaminoglycan chains: Implications for multiple myeloma

“…41: 437-449 DOI 10.1002 Innate immunity 437 biological function of SG is not fully elucidated, but the results obtained from studies with SG-knockout mice suggest a role for SG in the delivery of proteins into secretory granules and/or directing the secretion of these molecules [2]. It appears that SG interacts with a plethora of molecules, playing a role in the delivery of these components into secretory vesicles and further into their targets via its highly negatively charged GAG chains.Other studies have demonstrated that SG plays a key role in the storage of mast cell proteases and granzyme B and the maturation of secretory granules of mast cells and cytotoxic T-cells [7,8]. Furthermore, SG plays a crucial role in cytotoxic T-cells, as part of a multimolecular complex with perforin and granzyme B, in the delivery of the latter to the target cells during cytotoxic cell-granule-mediated cell death [9].…”

“…Other studies have demonstrated that SG plays a key role in the storage of mast cell proteases and granzyme B and the maturation of secretory granules of mast cells and cytotoxic T-cells [7,8]. Furthermore, SG plays a crucial role in cytotoxic T-cells, as part of a multimolecular complex with perforin and granzyme B, in the delivery of the latter to the target cells during cytotoxic cell-granule-mediated cell death [9].…”

Serglycin proteoglycan in hematologic malignancies: a marker of acute myeloid leukemia

“…3,[11][12][13]15 We have shown that serglycin is present in promyelocytes and disappears as cells mature along the granulocytic lineage during normal myelopoiesis. 9 This prompted us to explore the expression of serglycin proteoglycan in bone marrow of AML patients and to compare with ALL patients and normal controls.…”

“…11,12 More recently, serglycin proved to be essential both for maturation of mast cell granules and for localization of granule proteins. 13 Furthermore, granzyme B was shown to be delivered from cytotoxic lymphocytes to target cells as a macromolecular complex with serglycin. 14 The amount of granzyme B but not granzyme A nor perforin in granules is reduced in T cells lacking serglycin and the ultrastructure of granules is slightly altered.…”