Subcellular trafficking and activity of hyal-1 and its processed forms in murine macrophages

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The hyaluronidase Hyal-1 is an acid hydrolase that degrades hyaluronic acid (HA), a component of the extracellular matrix. It is often designated as a lysosomal protein. Yet few data are available on its intracellular localization and trafficking. We demonstrate here that in RAW264.7 murine macrophages, Hyal-1 is synthesized as a glycosylated precursor that is only weakly mannose 6-phosphorylated. Nevertheless, this precursor traffics to endosomes, via a mannose 6-phosphate-independent secretion/recapture mechanism that involves the mannose receptor. Once in endosomes, it is processed into a lower molecular mass form that is transported to lysosomes, where its activity could be detected using native gel zymography. Indeed, this activity co-distributed with lysosomal hydrolases in the densest fraction of a self-forming PercollTM density gradient. Moreover, it shifted toward the lower density region, in parallel with those hydrolases, when a decrease of lysosomal density was induced by the endocytosis of sucrose. Interestingly, the activity of the processed form of Hyal-1 was largely underestimated when assayed by zymography after SDS-PAGE and subsequent renaturation of the proteins, by contrast to the full-length protein that could efficiently degrade HA in those conditions. These results suggest that noncovalent associations support the lysosomal activity of Hyal-1.

Original languageEnglish
Pages (from-to)500-15
Number of pages16
JournalTraffic (Copenhagen, Denmark)
Issue number5
Early online date6 Feb 2014
Publication statusPublished - 2014


  • Animals
  • Endocytosis
  • Endosomes
  • Glycosylation
  • Hyaluronoglucosaminidase
  • Hydrolases
  • Lectins, C-Type
  • Lysosomes
  • Macrophages
  • Mannose-Binding Lectins
  • Mannosephosphates
  • Mice
  • Protein Transport
  • Receptors, Cell Surface
  • Sucrose


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