| First Author | Sohar I | Year | 1998 |
| Journal | Biochem J | Volume | 330 ( Pt 2) |
| Pages | 903-8 | PubMed ID | 9480908 |
| Mgi Jnum | J:46982 | Mgi Id | MGI:1202462 |
| Doi | 10.1042/bj3300903 | Citation | Sohar I, et al. (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. Biochem J 330(Pt 2):903-8 |
| abstractText | 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 B-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 similar to 45-fold and similar to 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. |
