| First Author | Kowalewski B | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 40 | Pages | 27992-8005 |
| PubMed ID | 25135642 | Mgi Jnum | J:306884 |
| Mgi Id | MGI:6709386 | Doi | 10.1074/jbc.M114.584144 |
| Citation | Kowalewski B, et al. (2014) Molecular characterization of arylsulfatase G: expression, processing, glycosylation, transport, and activity. J Biol Chem 289(40):27992-8005 |
| abstractText | Arylsulfatase G (ARSG) is a recently identified lysosomal sulfatase that was shown to be responsible for the degradation of 3-O-sulfated N-sulfoglucosamine residues of heparan sulfate glycosaminoglycans. Deficiency of ARSG leads to a new type of mucopolysaccharidosis, as described in a mouse model. Here, we provide a detailed molecular characterization of the endogenous murine enzyme. ARSG is expressed and proteolytically processed in a tissue-specific manner. The 63-kDa single-chain precursor protein localizes to pre-lysosomal compartments and tightly associates with organelle membranes, most likely the endoplasmic reticulum. In contrast, proteolytically processed ARSG fragments of 34-, 18-, and 10-kDa were found in lysosomal fractions and lost their membrane association. The processing sites and a disulfide bridge between the 18- and 10-kDa chains could be roughly mapped. Proteases participating in the processing were identified as cathepsins B and L. Proteolytic processing is dispensable for hydrolytic sulfatase activity in vitro. Lysosomal transport of ARSG in the liver is independent of mannose 6-phosphate, sortilin, and Limp2. However, mutation of glycosylation site N-497 abrogates transport of ARSG to lysosomes in human fibrosarcoma cells, due to impaired mannose 6-phosphate modification. |
