Cation-dependent mannose-6-phosphate receptor (CD-MPR) (CD-MPR)

The Cation-dependent mannose-6-phosphate receptor (CD-MPR), also known as MPR 46, is a 46 kDa transmembrane glycoprotein that functions as a P-type lectin essential for the trafficking of lysosomal enzymes (UniProt P20645). It specifically recognizes the mannose-6-phosphate (M6P) recognition marker on newly synthesized acid hydrolases within the trans-Golgi network, facilitating their transport to the endosomal-lysosomal system (Ghosh et al., 2003). Unlike the larger cation-independent mannose-6-phosphate receptor (CI-MPR), the CD-MPR requires divalent cations, particularly manganese, for ligand binding and typically functions as a homodimer (NCBI Gene ID 4071). In the pharmaceutical industry, the M6P receptor pathway is the primary target for enzyme replacement therapies (ERTs) designed to treat lysosomal storage diseases such as Pompe disease and various mucopolysaccharidoses (Coutinho et al., 2012). Recombinant enzymes, including Alglucosidase alfa and Laronidase, are glycosylated with M6P residues to facilitate their uptake into cells and subsequent delivery to the lysosome via these receptors (Gary-Bobo et al., 2007). While the cation-independent receptor is the major mediator of endocytosis from the cell surface, the CD-MPR is a critical component of the overall transport machinery. Challenges in targeting this receptor include the development of neutralizing antibodies and the difficulty of achieving therapeutic concentrations in hard-to-reach tissues like the brain and bone.

Other names

MPR 4646 kDa mannose 6-phosphate receptorM6PRCD-M6PRSmall mannose 6-phosphate receptor

The receptor binds to mannose-6-phosphate (M6P) moieties on lysosomal enzymes in a cation-dependent manner (requiring divalent cations like Mn2+), facilitating their sorting from the trans-Golgi network to endosomes and mediating the endocytic uptake of extracellular enzymes (Ghosh et al., 2003; Gary-Bobo et al., 2007).