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. 2020 Nov 7;10(11):1525. doi: 10.3390/biom10111525

Figure 4.

Figure 4

Schematic illustration of HA degradation mechanisms. In HYAL-mediated HA degradation (top), HMW HA is tethered to the cell surface by CD44 and GPI-anchored HYAL2 into caveolin-rich lipid rafts and then cleaved into approximately 2 × 104 Da fragments. The HA fragments are subsequently delivered to endo-lysosome compartments and degraded into smaller oligosaccharides by HYAL1 and monosaccharides by exoglycosidases. In the proposed model of CEMIP-mediated HA degradation (bottom), HMW HA is endocytosed into clathrin-coated vesicles and cleaved into lower molecular weight HA fragments by the action of CEMIP, which is localized in the peripheral vesicles of the cell. The fragmented HA is then depolymerized in endo-lysosome compartments or released extracellularly without intracytoplasmic accumulation. TMEM2 is expressed on the cell surface in a type II transmembrane topology and degrades HMW HA into approximately 5 × 103 Da fragments.