Two proteins have been implicated in the mannose 6-phosphate-dependent transport of lysosomal enzymes to lysosomes: the 300 kDa cation-independent and the 46 kDa cation-dependent mannose 6-phosphate receptors (CI- and CD-MPRs). The mammalian CI-MPR also mediates endocytosis and clearance of insulin-like growth factor II (IGF-II). Mutant mice that lack the CD-MPR are viable, mice that lack the CI-MPR accumulate high levels of IGF-II and usually die perinatally, whereas mice that lack both IGF-II and CI-MPR are viable. To investigate the relative roles of the MPRs in the targeting of lysosomal enzymes in vivo, we analysed the effect of a deficiency of either MPR on lysosomal enzyme activities in animals lacking IGF-II. In CD-MPR-deficient mice, most activities were relatively normal in solid tissues and some were marginally elevated in serum. In CI-MPR-deficient mice, some enzyme activities were moderately decreased in solid tissues and multiple enzymes were markedly elevated in serum. Finally, total levels of serum mannose 6-phosphorylated glycoproteins were ~ 45-fold and ~ 15-fold higher than wild type in CI- and CD-MPR-deficient mice respectively, and there were specific differences in the pattern of these proteins when comparing CI- and CD-MPR deficient animals. These results indicate that while lack of the CI-MPR appears to perturb lysosome function to a greater degree than lack of the CD-MPR, each MPR has distinct functions for the targeting of lysosomal enzymes in vivo.
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March 1998
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Research Article|
March 01 1998
Mouse mutants lacking the cation-independent mannose 6-phosphate/insulin-like growth factor II receptor are impaired in lysosomal enzyme transport: comparison of cation-independent and cation-dependent mannose 6-phosphate receptor-deficient mice Available to Purchase
Istvan SOHAR;
Istvan SOHAR
*Center for Advanced Biotechnology and Medicine and Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, U.S.A.
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David SLEAT;
David SLEAT
*Center for Advanced Biotechnology and Medicine and Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, U.S.A.
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Chang-Gong LIU;
Chang-Gong LIU
*Center for Advanced Biotechnology and Medicine and Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, U.S.A.
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Thomas LUDWIG;
Thomas LUDWIG
†Department of Anatomy and Cell Biology, Columbia University, New York, NY 10032, U.S.A.
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Peter LOBEL
Peter LOBEL
1
*Center for Advanced Biotechnology and Medicine and Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, U.S.A.
1To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Received:
September 01 1997
Revision Received:
October 31 1997
Accepted:
November 14 1997
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1998
1998
Biochem J (1998) 330 (2): 903–908.
Article history
Received:
September 01 1997
Revision Received:
October 31 1997
Accepted:
November 14 1997
Citation
Istvan SOHAR, David SLEAT, Chang-Gong LIU, Thomas LUDWIG, Peter LOBEL; Mouse mutants lacking the cation-independent mannose 6-phosphate/insulin-like growth factor II receptor are impaired in lysosomal enzyme transport: comparison of cation-independent and cation-dependent mannose 6-phosphate receptor-deficient mice. Biochem J 1 March 1998; 330 (2): 903–908. doi: https://doi.org/10.1042/bj3300903
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