This article is about the cation-dependent mannose 6-phosphate receptor. For the cation-independent mannose 6-phosphate receptor, see Insulin-like growth factor 2 receptor.
In the fields of biochemistry and cell biology, the cation-dependent mannose-6-phosphate receptor (CD-MPR) also known as the 46 kDa mannose 6-phosphate receptor is a protein that in humans is encoded by the M6PRgene.[1][2]
The CD-MPR is a type I transmembrane protein (that is, it has a single transmembrane domain with its C-termini on the cytoplasmic side of lipid membranes) with a relatively short cytoplasmic tail.[3] The extracytoplasmic/lumenal M6P binding-domain consists of 157 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 insulin-like growth factor 2 also functions as a cation-independent mannose 6-phosphate receptor.[3] 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 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 divalent cations, such as manganese.[3] The MPRs (bound to their cargo) are recognized by the GGA family of clathrin adaptor proteins and accumulate in forming clathrin-coated vesicles.[4] They are trafficked to the early endosome where, in the relatively low 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.
↑ 3.03.13.2Ghosh P, Dahms NM, Kornfeld S (March 2003). "Mannose 6-phosphate receptors: new twists in the tale". Nat. Rev. Mol. Cell Biol. 4 (3): 202–12. doi:10.1038/nrm1050. PMID12612639.
↑Ghosh P, Kornfeld S (July 2004). "The GGA proteins: key players in protein sorting at the trans-Golgi network". Eur. J. Cell Biol. 83 (6): 257–62. doi:10.1078/0171-9335-00374. PMID15511083.
Further reading
Yang EB, Qin LL, Zhao YN, Zhang K, Chow P (2003). "Genetic changes and expression of the mannose 6-phosphate/insulin-like growth factor II receptor gene in human hepatitis B virus-associated hepatocellular carcinoma". Int. J. Mol. Med. 11 (6): 773–8. doi:10.3892/ijmm.11.6.773. PMID12736721.
Shin BK, Wang H, Yim AM, Le Naour F, Brichory F, Jang JH, Zhao R, Puravs E, Tra J, Michael CW, Misek DE, Hanash SM (2003). "Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function". J. Biol. Chem. 278 (9): 7607–16. doi:10.1074/jbc.M210455200. PMID12493773.
Lemansky P, Fester I, Smolenova E, Uhländer C, Hasilik A (2007). "The cation-independent mannose 6-phosphate receptor is involved in lysosomal delivery of serglycin". J. Leukoc. Biol. 81 (4): 1149–58. doi:10.1189/jlb.0806520. PMID17210618.
Doray B, Bruns K, Ghosh P, Kornfeld S (2002). "Interaction of the cation-dependent mannose 6-phosphate receptor with GGA proteins". J. Biol. Chem. 277 (21): 18477–82. doi:10.1074/jbc.M201879200. PMID11886874.
Schimanski LM, Drakesmith H, Sweetland E, Bastin J, Rezgui D, Edelmann M, Kessler B, Merryweather-Clarke AT, Robson KJ, Townsend AR (2009). "In vitro binding of HFE to the cation-independent mannose-6 phosphate receptor". Blood Cells Mol. Dis. 43 (2): 180–93. doi:10.1016/j.bcmd.2009.03.010. PMID19487139.
Kölsch H, Ptok U, Majores M, Schmitz S, Rao ML, Maier W, Heun R (2004). "Putative association of polymorphism in the mannose 6-phosphate receptor gene with major depression and Alzheimer's disease". Psychiatr. Genet. 14 (2): 97–100. doi:10.1097/01.ypg.0000129204.58574.c2. PMID15167696.
Xaplanteri P, Lagoumintzis G, Dimitracopoulos G, Paliogianni F (2009). "Synergistic regulation of Pseudomonas aeruginosa-induced cytokine production in human monocytes by mannose receptor and TLR2". Eur. J. Immunol. 39 (3): 730–40. doi:10.1002/eji.200838872. PMID19197942.
Hille-Rehfeld A (1995). "Mannose 6-phosphate receptors in sorting and transport of lysosomal enzymes". Biochim. Biophys. Acta. 1241 (2): 177–94. doi:10.1016/0304-4157(95)00004-b. PMID7640295.
Munier-Lehmann H, Mauxion F, Hoflack B (1996). "Function of the two mannose 6-phosphate receptors in lysosomal enzyme transport". Biochem. Soc. Trans. 24 (1): 133–6. PMID8674621.
Mari M, Bujny MV, Zeuschner D, Geerts WJ, Griffith J, Petersen CM, Cullen PJ, Klumperman J, Geuze HJ (2008). "SNX1 defines an early endosomal recycling exit for sortilin and mannose 6-phosphate receptors". Traffic. 9 (3): 380–93. doi:10.1111/j.1600-0854.2007.00686.x. PMID18088323.
Op den Brouw ML, Binda RS, Geijtenbeek TB, Janssen HL, Woltman AM (2009). "The mannose receptor acts as hepatitis B virus surface antigen receptor mediating interaction with intrahepatic dendritic cells". Virology. 393 (1): 84–90. doi:10.1016/j.virol.2009.07.015. PMID19683778.
Nair P, Schaub BE, Rohrer J (2003). "Characterization of the endosomal sorting signal of the cation-dependent mannose 6-phosphate receptor". J. Biol. Chem. 278 (27): 24753–8. doi:10.1074/jbc.M300174200. PMID12697764.
Kato N, Miyata T, Tabara Y, Katsuya T, Yanai K, Hanada H, Kamide K, Nakura J, Kohara K, Takeuchi F, Mano H, Yasunami M, Kimura A, Kita Y, Ueshima H, Nakayama T, Soma M, Hata A, Fujioka A, Kawano Y, Nakao K, Sekine A, Yoshida T, Nakamura Y, Saruta T, Ogihara T, Sugano S, Miki T, Tomoike H (2008). "High-density association study and nomination of susceptibility genes for hypertension in the Japanese National Project". Hum. Mol. Genet. 17 (4): 617–27. doi:10.1093/hmg/ddm335. PMID18003638.
Chen JJ, Zhu Z, Gershon AA, Gershon MD (2004). "Mannose 6-phosphate receptor dependence of varicella zoster virus infection in vitro and in the epidermis during varicella and zoster". Cell. 119 (7): 915–26. doi:10.1016/j.cell.2004.11.007. PMID15620351.
