Extracellular processing of the cartilage proteoglycan aggregate and its effect on CD44-mediated internalization of hyaluronan.

The Journal of Biological Chemistry
Ben T DanielsonW Knudson

Abstract

In many cells hyaluronan receptor CD44 mediates the endocytosis of hyaluronan and its delivery to endosomes/lysosomes. The regulation of this process remains largely unknown. In most extracellular matrices hyaluronan is not present as a free polysaccharide but often is found in complex with other small proteins and macromolecules such as proteoglycans. This is especially true in cartilage, where hyaluronan assembles into an aggregate structure with the large proteoglycan termed aggrecan. In this study when purified aggrecan was added to FITC-conjugated hyaluronan, no internalization of hyaluronan was detected. This suggested that the overall size of the aggregate prevented hyaluronan endocytosis and furthermore that proteolysis of the aggrecan was a required prerequisite for local, cell-based turnover of hyaluronan. To test this hypothesis, limited C-terminal digestion of aggrecan was performed to determine whether a size range of aggrecan exists that permits hyaluronan endocytosis. Our data demonstrate that only limited degradation of the aggrecan monomer was required to allow for hyaluronan internalization. When hyaluronan was combined with partially degraded, dansyl chloride-labeled aggrecan, blue fluorescent aggrecan was al...Continue Reading

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Citations

Apr 21, 2016·Matrix Biology : Journal of the International Society for Matrix Biology·Yi HuangWarren Knudson
Jan 1, 2008·Irish Veterinary Journal·Jml Hughes
Sep 14, 2018·International Journal of Molecular Sciences·Mikko J LammiChengjuan Qu
Jul 6, 2019·Seminars in Cancer Biology·Spyros S SkandalisParaskevi Heldin
Feb 19, 2019·Archives of Biochemistry and Biophysics·Kenya TerabeWarren Knudson
Oct 6, 2017·Matrix Biology : Journal of the International Society for Matrix Biology·Yeojung KimCarol A de la Motte

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