Cation-dependent mannose-6-phosphate receptor

In the fields of is_associated_with::biochemistry and is_associated_with::cell biology, the cation-dependent mannose-6-phosphate receptor (CD-MPR) also known as the 46 kDa mannose 6-phosphate receptor is a is_associated_with::protein that in humans is encoded by the M6PR is_associated_with::gene.

The CD-MPR is one of two is_associated_with::transmembrane proteins that bind is_associated_with::mannose-6-phosphate (M6P) tags on is_associated_with::acid hydrolase precursors in the is_associated_with::Golgi apparatus that are destined for transport to the is_associated_with::lysosome. Homologues of CD-MPR are found in all is_associated_with::eukaryotes.

Structure
The CD-MPR is a type I transmembrane protein (that is, it has a single transmembrane domain with its C-termini on the is_associated_with::cytoplasmic side of lipid membranes) with a relatively short cytoplasmic tail. The extracytoplasmic/lumenal M6P binding-domain consists of 157 is_associated_with::amino acid residues. The CD-MPR is approximately 46 kDa in size and it both exists and functions as a dimer.

The cell surface receptor for is_associated_with::insulin-like growth factor 2 also functions as a cation-independent mannose 6-phosphate receptor. It consists of fifteen repeats homologous to the 157-residue CD-M6PR domain, two of which are responsible for binding to M6P.

Function
Both CD-MPRs and CI-MPRs are is_associated_with::lectins that bind their M6P-tagged cargo in the lumen of the Golgi apparatus. The CD-MPR shows greatly enhanced binding to M6P in the presence of is_associated_with::divalent cations, such as is_associated_with::manganese. The MPRs (bound to their cargo) are recognized by the GGA family of is_associated_with::clathrin adaptor proteins and accumulate in forming clathrin-coated vesicles. They are trafficked to the early is_associated_with::endosome where, in the relatively low is_associated_with::pH environment of the endosome, 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 independently of the MPRs.