Document Detail


Disturbed cholesterol traffic but normal proteolytic function in LAMP-1/LAMP-2 double-deficient fibroblasts.
MedLine Citation:
PMID:  15121881     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mice double deficient in LAMP-1 and -2 were generated. The embryos died between embryonic days 14.5 and 16.5. An accumulation of autophagic vacuoles was detected in many tissues including endothelial cells and Schwann cells. Fibroblast cell lines derived from the double-deficient embryos accumulated autophagic vacuoles and the autophagy protein LC3II after amino acid starvation. Lysosomal vesicles were larger and more peripherally distributed and showed a lower specific density in Percoll gradients in double deficient when compared with control cells. Lysosomal enzyme activities, cathepsin D processing and mannose-6-phosphate receptor expression levels were not affected by the deficiency of both LAMPs. Surprisingly, LAMP-1 and -2 deficiencies did not affect long-lived protein degradation rates, including proteolysis due to chaperone-mediated autophagy. The LAMP-1/2 double-deficient cells and, to a lesser extent, LAMP-2 single-deficient cells showed an accumulation of unesterified cholesterol in endo/lysosomal, rab7, and NPC1 positive compartments as well as reduced amounts of lipid droplets. The cholesterol accumulation in LAMP-1/2 double-deficient cells could be rescued by overexpression of murine LAMP-2a, but not by LAMP-1, highlighting the more prominent role of LAMP-2. Taken together these findings indicate partially overlapping functions for LAMP-1 and -2 in lysosome biogenesis, autophagy, and cholesterol homeostasis.
Authors:
Eeva-Liisa Eskelinen; Christine Katrin Schmidt; Silja Neu; Marion Willenborg; Graciela Fuertes; Natalia Salvador; Yoshitaka Tanaka; Renate Lüllmann-Rauch; Dieter Hartmann; Jörg Heeren; Kurt von Figura; Erwin Knecht; Paul Saftig
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-04-30
Journal Detail:
Title:  Molecular biology of the cell     Volume:  15     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-25     Completed Date:  2005-01-31     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3132-45     Citation Subset:  IM    
Affiliation:
Institute of Biochemistry, University of Kiel, D-24098 Kiel, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD / genetics,  metabolism,  physiology*
Cells, Cultured
Cholesterol / analysis,  metabolism*
Cytoplasmic Vesicles / immunology,  physiology*,  ultrastructure
Embryo, Mammalian / metabolism
Fibroblasts / chemistry,  immunology,  metabolism
Filipin / analysis,  chemistry
Lysosome-Associated Membrane Glycoproteins
Lysosomes / enzymology,  ultrastructure
Mice
Mice, Knockout
Proteins / analysis
rab GTP-Binding Proteins / analysis,  genetics,  metabolism
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Lysosome-Associated Membrane Glycoproteins; 0/Npc1 protein, mouse; 0/Proteins; 152989-05-4/rab7 protein; 480-49-9/Filipin; 57-88-5/Cholesterol; EC 3.6.1.-/rab GTP-Binding Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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