Molecular Biology of Mast Cell Secretory Granule Proteoglycans and Proteases
Mast cells and a large number of other hematopoietic cells have secretory granules which contain a unique family of proteoglycans. In the case of the roast cell, these proteoglycans are exocytosed when the IgE receptors on the cell’s plasma membrane are cross-linked with antigen (Yurt et al. 1977). While a number of functions haive been attributed to secretory granule proteoglycans of hematopoietic cells, it appears that a major function is to interact specifically with basically charged secretory granule proteins (Yurt and Austen 1977; Serafin et al. 1986). Mast cells have been found to contain large amounts of basically charged serine proteases that are enzymatically active at neutral pH (Woodbury et al. 1978; Schwartz et al. 1981; Dubuske et al. 1984; Shechter et al. 1986; LeTrong et al. 1987). In the rat serosal mast cell (Everitt and Neurath 1980), the mouse bone marrow-derived mast cell (BMMC) (Serafin et al. 1987), and the human skin mast cell (Goldstein et al. 1987)], the proteoglycans and serine proteases have been shown to be also packaged with basically charged carboxypeptidases. These endopeptidases and exopeptidases are stored in active form in secretory granules, and therefore it is likely that one of the functions of proteoglycans in mast cells is to package the enzymes in a configuration that minimizes their autolysis. When the composition of the protease/proteoglycan macromolecular complex in the mouse BMMC was examined during the stage of differentiation in which the cell was synthesizing both chondroitin sulfate E proteoglycan and heparin proteoglycan, it was discovered that the macromolecular complex was preferentially enriched for heparin proteoglycans (Serafin et al. 1986). In addition, when different Kirsten sarcoma virus immortalized mast cell (KiSV-MC) lines were examined for their protease activities and biosynthesis of proteoglycans, a strong positive correlation was observed in carboxypeptidase A content and biosynthesis of heparin proteoglycans relative to chondroitin sulfate E proteoglycans (Reynolds et al. 1988). Thus for proteoglycans, the type of the glycosaminoglycan that is polymerized onto the serine/glycine-rich peptide core may be related to the type of protein with which the proteoglycan is to interact inside the secretory granule.
KeywordsMast Cell Secretory Granule Mouse Mast Cell Cell Secretory Granule Human Skin Mast Cell
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- Avraham S, Stevens RL, Nicodemus CF, Gartner MC, Austen KF, Weis JH (1989) Molecular cloning of a cDNA that encodes the peptide core of a mouse mast cell secretory granule proteoglycan and comparison with the analogous rat and human cDNA. Proc Natl Acad Sci 86:3763–3767PubMedCentralPubMedCrossRefGoogle Scholar
- Avraham S, Austen KF, Nicodemus CF, Gartner MCt Stevens RL Cloning and characterization of the mouse gene that encodes the peptide core of secretory granule proteoglycans, and expression of this gene in transfected rat-1 fibroblasts. J Biol Chem, in pressGoogle Scholar
- Benfey PN, Yin FH, Leder P (1987) Cloning of the mast cell protease, RMCP II. Evidence for cell-specific expression and a multi-gene family. J Biol Chem 262:5377–5384Google Scholar
- Reynolds DS, Serafin WE, Faller DV, Wall DA, Abbas AK, Dvorak AM, Austen KF, Stevens RL (1988) Immortalization of murine connective tissue-type mast cells at multiple stages of their differentiation by coculture of splenocytes with fibroblasts that produce Kirsten sarcoma virus. J Biol Chem 263:12783–12791PubMedGoogle Scholar
- Reynolds DS, Stevens RL, Austen KF, Serafin WE. (1989a) Molecular characterization of murine connective tissue mast cell neutral proteases. J Allegy Clin Immunol 83:216 (abstract)Google Scholar
- Reynolds DS, Stevens RL, Austen KF, Serafin WE. (1989b) Isolation and characterization of a cDNA that encodes a mouse mast cell carboxypeptidase A (CPA) — a prominent secretory granule enzyme of connective tissue-type mast cells (CTMC) FASEB J 3:A1276 (abstract)Google Scholar
- Sarid J, Benfey PN, and Leder P. (1989) The mast cell-specific expression of a protease gene, RMCP-II, is regulated by an enhancer element that binds specifically to mast cell trans-acting factors. J. Biol. Chem. 264:1022–1026Google Scholar
- Seldin DC, Adelman S, Austen KF, Stevens RL, Hein A, Caulfield JP, and Woodbury RG. (1985) Homology of the rat basophilic leukemia cell and the rat mucosal mast cell. Proc. Natl. Acad. Sci. USA 82:3871–3875Google Scholar
- Serafin WE, Dayton ET, Gravallese PM, Austen KF, Stevens RL (1987) Carboxypeptidase A in mouse mast cells: Identification, characterization, and use as a differentiation marker. J Immunol 139:3771–3776Google Scholar
- Yurt R, Austen KF (1977) Preparative purification of the rat mast cell chymase. Characterization and interaction with granule components. J Exp Med 146:1405–1419Google Scholar