Interaction of chondroitin sulfate with perforin and granzymes of cytolytic T-cells is dependent on pH

Details

Serval ID
serval:BIB_1B948326AC42
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Interaction of chondroitin sulfate with perforin and granzymes of cytolytic T-cells is dependent on pH
Journal
Biochemistry
Author(s)
Masson  D., Peters  P. J., Geuze  H. J., Borst  J., Tschopp  J.
ISSN
0006-2960 (Print)
Publication state
Published
Issued date
12/1990
Volume
29
Number
51
Pages
11229-35
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec 25
Abstract
Cytolytic T-lymphocytes (CTL) harbor cytoplasmic granules containing the lytic, pore-forming protein perforin, a family of serine proteases designated granzymes, and proteoglycans as major constituents. Growth of CTL lines in the presence of PNP-xyloside completely inhibited the glycosylation of the granule-associated chondroitin sulfate A type proteoglycans. Only short glycosaminoglycan molecules were detected. The absence of intact proteoglycans neither altered the sorting of the granule-associated proteins perforin or granzyme A nor influenced their secretion into the extracellular milieu upon T-cell receptor complex stimulation. With a weak base, the pH of the granules was determined to be acidic. At pH 5.2, granzyme A and perforin formed complexes with chondroitin sulfate A. At neutral pH, perforin and only a minor fraction of granzyme A dissociated from the proteoglycan. Upon secretion of the granule contents induced by immobilized anti-CD3 antibodies, most granzyme A molecules remained complexed with the chondroitin sulfate A glycosaminoglycans, even if synthesis of intact proteoglycans was inhibited. We suggest that granule-associated molecules complex with proteoglycans under the acidic conditions prevailing in the trans Golgi and cytolytic granules. A possible pH shift occurring during exocytosis would cause perforin, but only a minor fraction of granzyme A, to dissociate from the proteoglycans.
Keywords
Animals Cell Fractionation Cell Line Centrifugation, Zonal Chondroitin Sulfates/*metabolism Chromatography, Gel Clone Cells Cytoplasmic Granules/*metabolism/ultrastructure Humans Hydrogen-Ion Concentration Kinetics *Membrane Glycoproteins Membrane Proteins/*metabolism Mice Microscopy, Electron Molecular Weight Pore Forming Cytotoxic Proteins Proteoglycans/isolation & purification/metabolism Serine Endopeptidases/*metabolism T-Lymphocytes, Cytotoxic/*metabolism
Pubmed
Web of science
Create date
24/01/2008 15:19
Last modification date
20/08/2019 12:52
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