The Cation-Dependent Mannose 6-Phosphate Receptor

Abstract

The 46kDa cation-dependent mannose 6-phosphate receptor (CD-MPR) and the 300kDa cation-independent mannose 6-phosphate receptor (CI-MPR) are the sole members of the P-type family of lectins, which derive their name from their ability to bind phosphorylated mannose residues. The MPRs are found ubiquitously in higher eukaryotes, and most cell types express both receptors. A key function mediated by the MPRs is the targeting of newly synthesized soluble acid hydrolases bearing mannose 6-phosphate (Man-6-P) residues to the lysosome, an acidified organelle that is responsible for the degradation of both internalized and endogenous macromolecules (de Duve 1963). The generation of functional lysosomes is essential for the survival of the organism as evidenced by the autosomal recessive human lysosomal storage disorder, mucolipidosis II (I-cell disease; Neufeld 1991), a disease characterized by severe psychomotor retardation, hepatomegaly, and cardiomegaly that results in death within the first decade of life (Kornfeld and Sly 1995). I-cell disease is caused by the absence of the enzyme (i.e., phosphotransferase) which generates the Man-6-P recognition marker on lysosomal enzymes, resulting in the mistargeting of these enzymes into the secretory pathway. As expected, patients affected with this disease exhibit elevated levels of lysosomal enzymes in their serum and extracellular fluids and their cells contain numerous dense vacuoles filled with storage material.