Shedding of Cell Membrane-Bound Proteoglycans
Membrane-bound proteoglycans function primarily as coreceptors for many glycosaminoglycan (GAG)-binding ligands at the cell surface. The majority of membrane-bound proteoglycans can also function as soluble autocrine or paracrine effectors as their extracellular domains, replete with all GAG chains, are enzymatically cleaved and released from the cell surface by ectodomain shedding. In particular, the ectodomain shedding of syndecans, a major family of cell surface heparan sulfate proteoglycans, is an important posttranslational mechanism that modulates diverse pathophysiological processes. Syndecan shedding is a tightly controlled process that regulates the onset, progression, and resolution of various infectious and noninfectious inflammatory diseases. This review describes methods to induce and measure the shedding of cell membrane-bound proteoglycans, focusing on syndecan shedding as a prototypic example.
Key wordsSyndecan Glypican Heparan sulfate proteoglycan Sheddase Matrix metalloproteinase ADAM Inflammation Infection Host defense
The authors would like to thank past and present members of the Park laboratory for developing essential reagents and constantly improving the described procedures. This work was supported by NIH grants R01 HL094613 and R01 HL107472.
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