The egasyn gene affects the processing of oligosaccharides of lysosomal beta-glucuronidase in liver.
The accumulation of the relatively large amounts of beta-glucuronidase in microsomal fractions of normal mice depends on formation of complexes with the protein egasyn. Unexpectedly, it was found that the egasyn gene also affects the processing of beta-glucuronidase, which is segregated to lysosomes. In egasyn-positive mice lysosomal beta-glucuronidase from liver has a mean pI of 5.9 with a minor proportion at pI 5.4, whereas in egasyn-negative mice the proportion of the two lysosomal forms is reversed. Combined experiments measuring susceptibility to neuraminidase and to endoglycosidase H and specific binding to Ricinus communis lectin-agarose columns showed that the alterations in isoelectric point were associated with a decrease in complex oligosaccharides of lysosomal beta-glucuronidase in egasyn-positive mice. Since this alteration occurs not only in a congenic strain carrying the Eg0 gene but also in several other inbred strains that are homozygous for this gene, it is considered to be a genuine effect of the Eg gene rather than other genes that might regulate oligosaccharide processing. Also, the alteration is likely to be a result of direct physical interaction of the egasyn protein and lysosomal beta-glucuronidase, since a second lysosomal enzyme, beta-galactosidase, which does not form complexes with egasyn, is unaffected. The results suggest a model in which egasyn not only causes accumulation of beta-glucuronidase in the microsomal compartment but also acts upon the precursor to lysosomal beta-glucuronidase to alter its interaction with trans-Golgi-apparatus processing enzymes.
D000118:Acetylglucosaminidase / Q000494:pharmacology; D000818:Animals; D002265:Carboxylic Ester Hydrolases; D005690:Galactose / Q000032:analysis; D005796:Genes; D005966:Glucuronidase / Q000378:metabolism*; D007525:Isoelectric Focusing; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000201:enzymology; D008970:Molecular Weight; D009844:Oligosaccharides / Q000378:metabolism*; D013045:Species Specificity
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009844:Oligosaccharides; D002265:Carboxylic Ester Hydrolases; C009751:egasyn; D005966:Glucuronidase; D000118:Acetylglucosaminidase; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D005690:Galactose