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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2007-11-20
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pubmed:abstractText |
beta-glucocerebrosidase, the enzyme defective in Gaucher disease, is targeted to the lysosome independently of the mannose-6-phosphate receptor. Affinity-chromatography experiments revealed that the lysosomal integral membrane protein LIMP-2 is a specific binding partner of beta-glucocerebrosidase. This interaction involves a coiled-coil domain within the lumenal domain. beta-glucocerebrosidase activity and protein levels were severely decreased in LIMP-2-deficient mouse tissues. Analysis of fibroblasts and macrophages isolated from these mice indicated that the majority of beta-glucocerebrosidase was secreted. Missorting of beta-glucocerebrosidase was also evident in vivo, as protein and activity levels were significantly higher in sera from LIMP-2-deficient mice compared to wild-type. Reconstitution of LIMP-2 in LIMP-2-deficient fibroblasts led to a rescue of beta-glucocerebrosidase levels and distribution. LIMP-2 expression also led to lysosomal transport of a beta-glucocerebrosidase endoplasmic reticulum retention mutant. These data support a role for LIMP-2 as the mannose-6-phosphate-independent trafficking receptor for beta-glucocerebrosidase.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0092-8674
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
131
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
770-83
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pubmed:meshHeading |
pubmed-meshheading:18022370-Amino Acid Sequence,
pubmed-meshheading:18022370-Animals,
pubmed-meshheading:18022370-Antigens, CD36,
pubmed-meshheading:18022370-Cell Line,
pubmed-meshheading:18022370-Endoplasmic Reticulum,
pubmed-meshheading:18022370-Fibroblasts,
pubmed-meshheading:18022370-Gaucher Disease,
pubmed-meshheading:18022370-Glucosylceramidase,
pubmed-meshheading:18022370-Humans,
pubmed-meshheading:18022370-Lysosome-Associated Membrane Glycoproteins,
pubmed-meshheading:18022370-Lysosomes,
pubmed-meshheading:18022370-Macrophages,
pubmed-meshheading:18022370-Mannosephosphates,
pubmed-meshheading:18022370-Mice,
pubmed-meshheading:18022370-Molecular Sequence Data,
pubmed-meshheading:18022370-Protein Binding,
pubmed-meshheading:18022370-Protein Structure, Secondary,
pubmed-meshheading:18022370-Protein Transport,
pubmed-meshheading:18022370-Recombinant Proteins,
pubmed-meshheading:18022370-Sequence Alignment
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pubmed:year |
2007
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pubmed:articleTitle |
LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase.
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pubmed:affiliation |
Genzyme Corporation, 1 Mountain Road, Framingham, MA 01701, USA. david.reczek@genzyme.com
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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