| First Author | Marschner K | Year | 2011 |
| Journal | Science | Volume | 333 |
| Issue | 6038 | Pages | 87-90 |
| PubMed ID | 21719679 | Mgi Jnum | J:174054 |
| Mgi Id | MGI:5051840 | Doi | 10.1126/science.1205677 |
| Citation | Marschner K, et al. (2011) A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism. Science 333(6038):87-90 |
| abstractText | Mucolipidosis II is a severe lysosomal storage disorder caused by defects in the alpha and beta subunits of the hexameric N-acetylglucosamine-1-phosphotransferase complex essential for the formation of the mannose 6-phosphate targeting signal on lysosomal enzymes. Cleavage of the membrane-bound alpha/beta-subunit precursor by an unknown protease is required for catalytic activity. Here we found that the alpha/beta-subunit precursor is cleaved by the site-1 protease (S1P) that activates sterol regulatory element-binding proteins in response to cholesterol deprivation. S1P-deficient cells failed to activate the alpha/beta-subunit precursor and exhibited a mucolipidosis II-like phenotype. Thus, S1P functions in the biogenesis of lysosomes, and lipid-independent phenotypes of S1P deficiency may be caused by lysosomal dysfunction. |
