Cation-dependent mannose-6-phosphate receptor explained

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 M6PR gene.^{[1] [2]}

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

See also

• Mannose 6-phosphate receptor

Further reading

• Yang EB, Qin LL, Zhao YN, Zhang K, Chow P . 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 . 2003 . 12736721 . 10.3892/ijmm.11.6.773 .
• 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 . 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 . 2003 . 12493773 . 10.1074/jbc.M210455200 . free .
• Lemansky P, Fester I, Smolenova E, Uhländer C, Hasilik A . The cation-independent mannose 6-phosphate receptor is involved in lysosomal delivery of serglycin . J. Leukoc. Biol. . 81 . 4 . 1149–58 . 2007 . 17210618 . 10.1189/jlb.0806520 . 23934078 . free .
• Doray B, Bruns K, Ghosh P, Kornfeld S . Interaction of the cation-dependent mannose 6-phosphate receptor with GGA proteins . J. Biol. Chem. . 277 . 21 . 18477–82 . 2002 . 11886874 . 10.1074/jbc.M201879200 . free .
• Schimanski LM, Drakesmith H, Sweetland E, Bastin J, Rezgui D, Edelmann M, Kessler B, Merryweather-Clarke AT, Robson KJ, Townsend AR . In vitro binding of HFE to the cation-independent mannose-6 phosphate receptor . Blood Cells Mol. Dis. . 43 . 2 . 180–93 . 2009 . 19487139 . 10.1016/j.bcmd.2009.03.010 .
• Rodriguez-Gabin AG, Yin X, Si Q, Larocca JN . Transport of mannose-6-phosphate receptors from the trans Golgi network to endosomes requires Rab31 . Exp. Cell Res. . 315 . 13 . 2215–30 . 2009 . 19345684 . 2753287 . 10.1016/j.yexcr.2009.03.020 .
• Seaman MN . Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer . J. Cell Biol. . 165 . 1 . 111–22 . 2004 . 15078902 . 2172078 . 10.1083/jcb.200312034 .
• Kölsch H, Ptok U, Majores M, Schmitz S, Rao ML, Maier W, Heun R . Putative association of polymorphism in the mannose 6-phosphate receptor gene with major depression and Alzheimer's disease . Psychiatr. Genet. . 14 . 2 . 97–100 . 2004 . 15167696 . 10.1097/01.ypg.0000129204.58574.c2 . 20452956 .
• Xaplanteri P, Lagoumintzis G, Dimitracopoulos G, Paliogianni F . Synergistic regulation of Pseudomonas aeruginosa-induced cytokine production in human monocytes by mannose receptor and TLR2 . Eur. J. Immunol. . 39 . 3 . 730–40 . 2009 . 19197942 . 10.1002/eji.200838872 . 19749155 . free .
• Hille-Rehfeld A . Mannose 6-phosphate receptors in sorting and transport of lysosomal enzymes . Biochim. Biophys. Acta . 1241 . 2 . 177–94 . 1995 . 7640295 . 10.1016/0304-4157(95)00004-b .
• Pérez-Victoria FJ, Mardones GA, Bonifacino JS . Requirement of the Human GARP Complex for Mannose 6-phosphate-receptor-dependent Sorting of Cathepsin D to Lysosomes . Mol. Biol. Cell . 19 . 6 . 2350–62 . 2008 . 18367545 . 2397299 . 10.1091/mbc.E07-11-1189 .
• Munier-Lehmann H, Mauxion F, Hoflack B . Function of the two mannose 6-phosphate receptors in lysosomal enzyme transport . Biochem. Soc. Trans. . 24 . 1 . 133–6 . 1996 . 8674621 . 10.1042/bst0240133.
• Mari M, Bujny MV, Zeuschner D, Geerts WJ, Griffith J, Petersen CM, Cullen PJ, Klumperman J, Geuze HJ . SNX1 defines an early endosomal recycling exit for sortilin and mannose 6-phosphate receptors . Traffic . 9 . 3 . 380–93 . 2008 . 18088323 . 10.1111/j.1600-0854.2007.00686.x . 31922423 . free .
• Op den Brouw ML, Binda RS, Geijtenbeek TB, Janssen HL, Woltman AM . The mannose receptor acts as hepatitis B virus surface antigen receptor mediating interaction with intrahepatic dendritic cells . Virology . 393 . 1 . 84–90 . 2009 . 19683778 . 10.1016/j.virol.2009.07.015 .
• Nair P, Schaub BE, Rohrer J . Characterization of the endosomal sorting signal of the cation-dependent mannose 6-phosphate receptor . J. Biol. Chem. . 278 . 27 . 24753–8 . 2003 . 12697764 . 10.1074/jbc.M300174200 . free .
• 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 . High-density association study and nomination of susceptibility genes for hypertension in the Japanese National Project . Hum. Mol. Genet. . 17 . 4 . 617–27 . 2008 . 18003638 . 10.1093/hmg/ddm335 .
• Chen JJ, Zhu Z, Gershon AA, Gershon MD . 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 . 2004 . 15620351 . 10.1016/j.cell.2004.11.007 . 14582599 . free .

Notes and References

1. Dahms NM, Lobel P, Breitmeyer J, Chirgwin JM, Kornfeld S . 46 kd mannose 6-phosphate receptor: cloning, expression, and homology to the 215 kd mannose 6-phosphate receptor . Cell . 50 . 2 . 181–92 . July 1987 . 2954652 . 10.1016/0092-8674(87)90214-5 . 23842311 .
2. Pohlmann R, Nagel G, Schmidt B, Stein M, Lorkowski G, Krentler C, Cully J, Meyer HE, Grzeschik KH, Mersmann G . Cloning of a cDNA encoding the human cation-dependent mannose 6-phosphate-specific receptor . Proc. Natl. Acad. Sci. U.S.A. . 84 . 16 . 5575–9 . August 1987 . 2441386 . 298905 . 10.1073/pnas.84.16.5575 . 1987PNAS...84.5575P . free .
3. Ghosh P, Dahms NM, Kornfeld S . Mannose 6-phosphate receptors: new twists in the tale . Nat. Rev. Mol. Cell Biol. . 4 . 3 . 202–12 . March 2003 . 12612639 . 10.1038/nrm1050 . 16991464 .
4. Ghosh P, Kornfeld S . The GGA proteins: key players in protein sorting at the trans-Golgi network . Eur. J. Cell Biol. . 83 . 6 . 257–62 . July 2004 . 15511083 . 10.1078/0171-9335-00374 .