Publication Date:
2011-07-02
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marschner, Katrin -- Kollmann, Katrin -- Schweizer, Michaela -- Braulke, Thomas -- Pohl, Sandra -- New York, N.Y. -- Science. 2011 Jul 1;333(6038):87-90. doi: 10.1126/science.1205677.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21719679" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
CHO Cells
;
Cell Line
;
Cholesterol/*metabolism
;
Chondrocytes/cytology
;
Cricetinae
;
Cricetulus
;
Enzyme Precursors/chemistry/*metabolism
;
HeLa Cells
;
Humans
;
Lipid Metabolism
;
Lysosomes/enzymology/*metabolism/ultrastructure
;
Mannosephosphates/metabolism
;
Mice
;
Morphogenesis
;
Mucolipidoses/enzymology/genetics/metabolism/pathology
;
N-Acetylgalactosamine-4-Sulfatase/metabolism
;
Osteogenesis
;
Proprotein Convertases/genetics/*metabolism
;
Protein Subunits/chemistry/metabolism
;
RNA, Small Interfering
;
Serine Endopeptidases/genetics/*metabolism
;
Transferases (Other Substituted Phosphate Groups)/chemistry/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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