Serglycin: A Structural and Functional Chameleon with Wide Impact on Immune Cells

Abstract

Among the different proteoglycans expressed by mammals, serglycin is in most immune cells the dominating species. A unique property of serglycin is its ability to adopt highly divergent structures, because of glycosylation with variable types of glycosaminoglycans when expressed by different cell types. Recent studies of serglycin-deficient animals have revealed crucial functions for serglycin in a diverse array of immunological processes. However, its exact function varies to a large extent depending on the cellular context of serglycin expression. Based on these findings, serglycin is emerging as a structural and functional chameleon, with radically different properties depending on its exact cellular and immunological context.

Proteolytic Histone Modification by Mast Cell Tryptase, a Serglycin Proteoglycan-dependent Secretory Granule Protease

“…TNF), and anionic proteoglycans of serglycin type and various MC-specific proteases, the latter including tryptases, chymases, and carboxypeptidase A3 (2)(3)(4). Previous studies have shown that serglycin proteoglycan has a key regulatory role in maintaining the homeostasis of the secretory granules by forming complexes with the various granule proteases and bioactive amines, thereby promoting their storage within granules (5,6).…”

Serglycin Proteoglycan Promotes Apoptotic versus Necrotic Cell Death in Mast Cells

“…it is composed of a "core protein" to which highly sulfated and thereby negatively charged polysaccharides of glycosaminoglycan type are attached (1,2). Serglycin is a major component of secretory granules in many hematopoietic cell types (3-7) but has additionally been detected as a secretory product of non-hematopoietic cells (8).…”

Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis

“…The storage and activities of MC proteases are, to a large extent, influenced by serglycin (Pejler et al , 2009a ;Kolset and Pejler , 2011 ), a proteoglycan species composed of a small protein core to which strongly negatively charged side chains of heparin (or chondroitin sulfate) type are attached. Primarily, serglycin proteoglycans are known to serve as storage matrices for several of the MC proteases, including mMCP-4, mMCP-5, mMCP-6 and MC-CPA, as shown by the absence of these proteases in MCs from serglycin-deficient mice ( Å brink et al, 2004 ).…”