Mannose 6-phosphate receptor-dependent endocytosis of lysosomal enzymes is increased in sulfatide-storing kidney cells

Biol Chem. 2009 Jan;390(1):41-8. doi: 10.1515/BC.2009.009.


Metachromatic leukodystrophy is a lysosomal disorder caused by the deficiency of arylsulfatase A (ASA). This leads to the storage of the sphingolipid 3-O-sulfogalactosylceramide (sulfatide) in various cell types, such as renal tubular cells. Examination of mannose 6-phosphate receptor (MPR300)-dependent endocytosis revealed that uptake of lysosomal enzymes is more than two-fold increased in sulfatide-storing kidney cells. Expression of MPR300 and its internalization rate is increased in these cells, whereas the recycling rate is decreased. Similar alterations can be found for the transferrin receptor, indicating that sulfatide storage leads to a general alteration of the endocytotic pathway. These data allow calculating that the endosomal pool from which receptors can recycle is 1.4- to 2-fold increased in lipid-storing cells. Immunocytochemistry demonstrates that the MPR300 in lipid-storing cells does not co-localize with accumulated sulfatide, suggesting that the kinetics of internalization and recycling appear to be altered indirectly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebroside-Sulfatase / deficiency
  • Cerebroside-Sulfatase / metabolism
  • Cricetinae
  • Endocytosis*
  • Gene Expression Regulation
  • Humans
  • Kidney / cytology*
  • Kidney / metabolism*
  • Kidney Tubules / cytology
  • Kidney Tubules / metabolism
  • Kinetics
  • Lysosomes / enzymology*
  • Mice
  • Receptor, IGF Type 2 / metabolism*
  • Receptors, Transferrin / metabolism
  • Sulfoglycosphingolipids / metabolism*


  • Receptor, IGF Type 2
  • Receptors, Transferrin
  • Sulfoglycosphingolipids
  • Cerebroside-Sulfatase