A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism.
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A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism. / Marschner, Katrin; Kollmann, Katrin; Schweizer, Michaela; Braulke, Thomas; Pohl, Sandra.
In: SCIENCE, Vol. 333, No. 6038, 6038, 2011, p. 87-90.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism.
AU - Marschner, Katrin
AU - Kollmann, Katrin
AU - Schweizer, Michaela
AU - Braulke, Thomas
AU - Pohl, Sandra
PY - 2011
Y1 - 2011
N2 - Mucolipidosis II is a severe lysosomal storage disorder caused by defects in the ? and ? 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 ?/?-subunit precursor by an unknown protease is required for catalytic activity. Here we found that the ?/?-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 ?/?-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.
AB - Mucolipidosis II is a severe lysosomal storage disorder caused by defects in the ? and ? 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 ?/?-subunit precursor by an unknown protease is required for catalytic activity. Here we found that the ?/?-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 ?/?-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.
KW - Animals
KW - Humans
KW - Mice
KW - Lipid Metabolism
KW - CHO Cells
KW - Cricetinae
KW - Cricetulus
KW - Morphogenesis
KW - Hela Cells
KW - Cell Line
KW - RNA, Small Interfering
KW - Cholesterol/metabolism
KW - Chondrocytes/cytology
KW - Enzyme Precursors/chemistry/metabolism
KW - Lysosomes/enzymology/metabolism/ultrastructure
KW - Mannosephosphates/metabolism
KW - Mucolipidoses/enzymology/genetics/metabolism/pathology
KW - N-Acetylgalactosamine-4-Sulfatase/metabolism
KW - Osteogenesis
KW - Proprotein Convertases/genetics/metabolism
KW - Protein Subunits/chemistry/metabolism
KW - Serine Endopeptidases/genetics/metabolism
KW - Transferases (Other Substituted Phosphate Groups)/chemistry/metabolism
KW - Animals
KW - Humans
KW - Mice
KW - Lipid Metabolism
KW - CHO Cells
KW - Cricetinae
KW - Cricetulus
KW - Morphogenesis
KW - Hela Cells
KW - Cell Line
KW - RNA, Small Interfering
KW - Cholesterol/metabolism
KW - Chondrocytes/cytology
KW - Enzyme Precursors/chemistry/metabolism
KW - Lysosomes/enzymology/metabolism/ultrastructure
KW - Mannosephosphates/metabolism
KW - Mucolipidoses/enzymology/genetics/metabolism/pathology
KW - N-Acetylgalactosamine-4-Sulfatase/metabolism
KW - Osteogenesis
KW - Proprotein Convertases/genetics/metabolism
KW - Protein Subunits/chemistry/metabolism
KW - Serine Endopeptidases/genetics/metabolism
KW - Transferases (Other Substituted Phosphate Groups)/chemistry/metabolism
M3 - SCORING: Journal article
VL - 333
SP - 87
EP - 90
JO - SCIENCE
JF - SCIENCE
SN - 0036-8075
IS - 6038
M1 - 6038
ER -
