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Processing of heparanase is mediated by syndecan-1 cytoplasmic domain and involves syntenin and α-actinin.
- Source :
-
Cellular & Molecular Life Sciences . Nov2014, Vol. 71 Issue 22, p4457-4470. 14p. - Publication Year :
- 2014
-
Abstract
- 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 α actinin are essential for heparanase processing. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HEPARANASE
*SYNDECANS
*CYTOPLASM
*ACTININ
*METASTASIS
Subjects
Details
- Language :
- English
- ISSN :
- 1420682X
- Volume :
- 71
- Issue :
- 22
- Database :
- Academic Search Index
- Journal :
- Cellular & Molecular Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 99019260
- Full Text :
- https://doi.org/10.1007/s00018-014-1629-9