| First Author | Shteingauz A | Year | 2014 |
| Journal | Cell Mol Life Sci | Volume | 71 |
| Issue | 22 | Pages | 4457-70 |
| PubMed ID | 24788042 | Mgi Jnum | J:324696 |
| Mgi Id | MGI:6832352 | Doi | 10.1007/s00018-014-1629-9 |
| Citation | Shteingauz A, et al. (2014) Processing of heparanase is mediated by syndecan-1 cytoplasmic domain and involves syntenin and alpha-actinin. Cell Mol Life Sci 71(22):4457-70 |
| abstractText | Heparanase activity plays a decisive role in cell dissemination associated with cancer metastasis. Cellular uptake of heparanase is considered a pre-requisite for the delivery of latent 65-kDa heparanase to lysosomes and its subsequent proteolytic processing and activation into 8- and 50-kDa protein subunits by cathepsin L. Heparan sulfate proteoglycans, and particularly syndecan, are instrumental for heparanase uptake and activation, through a process that has been shown to occur independent of rafts. Nevertheless, the molecular mechanism underlying syndecan-mediated internalization outside of rafts is unclear. Here, we examined the role of syndecan-1 cytoplasmic domain in heparanase processing, utilizing deletion constructs lacking the entire cytoplasmic domain (Delta), the conserved (C1 or C2), or variable (V) regions. Heparanase processing was markedly increased following syndecan-1 over-expression; in contrast, heparanase was retained at the cell membrane and its processing was impaired in cells over-expressing syndecan-1 deleted for the entire cytoplasmic tail. We have next revealed that conserved domain 2 (C2) and variable (V) regions of syndecan-1 cytoplasmic tail mediate heparanase processing. Furthermore, we found that syntenin, known to interact with syndecan C2 domain, and alpha actinin are essential for heparanase processing. |
