Cation-dependent Mannose-6-phosphate receptor

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The mannose 6-phosphate receptor, also referred to as the cation-dependent mannose 6-phosphate receptor or CD-MPR, is one of two transmembrane proteins that bind mannose-6-phosphate (M6P) on lysosomal proteins in the Golgi apparatus that are destined for transport to the lysosome (1-6, 6, 7). The other protein is termed the cation-independent mannose-6-phosphate receptor or (CI-MPR) and is also the receptor for Insulin-like growth factor II (8-14). The CD-MPR is found in all eukaryotes and is known to play a highly conserved role in recognition and targeting of lysosomal enzymes. Both CD-MPRs and CI-MPRs are Glycan-binding proteins that bind their M6P-tagged cargo in the lumen of the Golgi apparatus (6). The CD-MPR shows enhanced binding to M6P in the presence of divalent cations, such as manganese (7, 15). Once bound to their cargo, the MPRs are recognized by the GGA family of clathrin adaptor proteins and accumulate in forming clathrin-coated vesicles. Upon arriving at the early endosome, the low pH environment of the endosome induces the MPRs release their cargo. The MPRs are recycled back to the Golgi, again by way of interaction with GGAs and vesicles. The cargo proteins are then trafficked to the lysosome via the late endosome in a process independent of the MPRs (6). Cargo molecules undergo extensive processing terminating in terminal mannose-6 phosphate on one or more arms of the oligosaccharide.

Contents

CFG Participating Investigators contributing to the understanding of this paradigm

CFG Participating Investigators (PIs) with interest in the Mannose-6-phosphate receptor include: Ajit Varki Non-PIs using CFG resources to study the Mannose-6-phosphate receptor include: Nancy Dahms

Progress toward understanding this GBP paradigm

Carbohydrate ligands


Cellular expression


Structure


Biological roles of GBP-ligand interaction


CFG resources used in investigations

The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for Mannose-6-phosphate.

Glycan profiling


Glycogene microarray


Knockout mouse lines


Glycan array

In 2006, soluble forms of the Mannose-6-phosphate receptor were screened on the CFG glycan array.

Related GBPs

The cation-independent Mannose-6-phosphate (CI-M-6-P) receptor has a shared motif with the CD-M-6-P receptor.

References


Acknowledgements

The CFG is grateful to the following PIs for their contributions to this wiki page:

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