Mannose 6-phosphate receptor

Mannose 6-phosphate receptor
Cation-independent mannose-6-phosphate receptor repeat
Identifiers
Symbol CIMR
Pfam PF00878
InterPro IPR000479
SCOP 1e6f
Cation-dependent mannose-6-phosphate receptor
Identifiers
Symbol M6PR
Entrez 4074
HUGO 6752
OMIM 154540
RefSeq NM_002355
UniProt P20645
Other data
Locus Chr. 12 p13
Cation-independent mannose-6 phosphate receptor
Identifiers
Symbol IGF2R
Entrez 3482
HUGO 5467
OMIM 147280
RefSeq NM_000876
UniProt P11717
Other data
Locus Chr. 6 q25q27

In the fields of biochemistry and cell biology, mannose 6-phosphate receptors (MPRs) are proteins that bind newly synthesized lysosomal hydrolases in the trans-Golgi network (TGN) and deliver them to pre-lysosomal compartments. There are two different MPRs, one of ~300kDa and a smaller, dimeric receptor of ~46kDa.[1][2] The larger receptor is known as the cation-independent mannose 6-phosphate receptor (CI-MPR), while the smaller receptor (CD-MPR) requires divalent cations to efficiently recognize lysosomal hydrolases.[2] While divalent cations are not essential for ligand binding by the human CD-MPR, the nomenclature has been retained.[3]

Both of these receptors bind terminal mannose 6-phosphate with similar affinity (CI-MPR = 7 μM, CD-MPR = 8 μM)[4] and have similar signals in their cytoplasmic domains for intracellular trafficking.[5]

Contents

Function

Early in the Golgi, the oligosaccharide chains of lysosomal hydrolases are tagged with terminal phosphomannosyl moieties.[6][7] The lysosomal hydrolases continue through the Golgi and encounter MPRs at the TGN.[8]

At the TGN, MPR-ligand complexes interact with the heterotetrameric complex of the AP1 clathrin adaptor complex[9] and/or members of the GGA family[10][11] of clathrin adapters. Binding concentrates receptor-ligand complexes into tubular structures at the TGN [12] and they are packaged into clathrin-coated vesicles.[13] These vesicles are very dynamic and live-cell video microscopy shows that they fuse with early endosomes that are positive for internalized transferrin.[12] MPRs are then segregated from transferrin within early endosomes, yielding two distinct domains.[12]

Recycling to the trans-Golgi network

The return route taken by MPRs to the TGN has been somewhat controversial. Because depletion of AP1[14] or so-called retromer proteins[15] results in MPR sequestration in early endosomes, many have concluded that the MPR traffics directly from early endosomes to the TGN. The bacterial shiga toxin[16] and cholera toxins[17] use such a pathway while TGN46[18] recycles back to the Golgi via recycling endosomes. However, MPRs bind their ligands in a pH dependent manner and need a pH < 6 to dissociate the ligand from the MPR.[19] The pH of the early endosome has been measured to be between pH 6.2-6.3, while the pH of the late endosome is pH 5.2-5.8; this was measured using the intensity ratio of fluorescein.[20] RAB9A is a late endosomal Rab protein that is absolutely required for MPR retrieval.[21] In addition, Press et al. (1998) [22] showed that the late endosome Rab7 was required for proper MPR trafficking. When they expressed inactive Rab7 in cells, the MPR was trapped in an early endosomes and could not return to the TGN [22]. More recent work has also confirmed the role that Rab7 plays in proper retromer localization and function.[23][24] Thus, the MPR must pass through the late endosome to dissociate lysosomal hydrolases before return to the TGN.

References

  1. ^ Hoflack B, Kornfeld S (July 1985). "Lysosomal enzyme binding to mouse P388D1 macrophage membranes lacking the 215-kDa mannose 6-phosphate receptor: evidence for the existence of a second mannose 6-phosphate receptor". Proc. Natl. Acad. Sci. U.S.A. 82 (13): 4428–32. doi:10.1073/pnas.82.13.4428. PMC 391114. PMID 3160044. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=391114. 
  2. ^ a b Hoflack B, Kornfeld S (October 1985). "Purification and characterization of a cation-dependent mannose 6-phosphate receptor from murine P388D1 macrophages and bovine liver". J. Biol. Chem. 260 (22): 12008–14. PMID 2931431. 
  3. ^ Junghans U, Waheed A, von Figura K (September 1988). "The 'cation-dependent' mannose 6-phosphate receptor binds ligands in the absence of divalent cations". FEBS Lett. 237 (1–2): 81–4. doi:10.1016/0014-5793(88)80176-5. PMID 2971570. 
  4. ^ Tong PY, Kornfeld S (May 1989). "Ligand interactions of the cation-dependent mannose 6-phosphate receptor. Comparison with the cation-independent mannose 6-phosphate receptor". J. Biol. Chem. 264 (14): 7970–5. PMID 2542255. 
  5. ^ Johnson KF, Chan W, Kornfeld S (December 1990). "Cation-dependent mannose 6-phosphate receptor contains two internalization signals in its cytoplasmic domain". Proc. Natl. Acad. Sci. U.S.A. 87 (24): 10010–4. doi:10.1073/pnas.87.24.10010. PMC 55304. PMID 2175900. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=55304. 
  6. ^ Reitman ML, Kornfeld S (December 1981). "Lysosomal enzyme targeting. N-Acetylglucosaminylphosphotransferase selectively phosphorylates native lysosomal enzymes". J. Biol. Chem. 256 (23): 11977–80. PMID 6457829. 
  7. ^ Waheed A, Hasilik A, von Figura K (October 1982). "UDP-N-acetylglucosamine:lysosomal enzyme precursor N-acetylglucosamine-1-phosphotransferase. Partial purification and characterization of the rat liver Golgi enzyme". J. Biol. Chem. 257 (20): 12322–31. PMID 6288715. 
  8. ^ Duncan JR, Kornfeld S (March 1988). "Intracellular movement of two mannose 6-phosphate receptors: return to the Golgi apparatus". J. Cell Biol. 106 (3): 617–28. doi:10.1083/jcb.106.3.617. PMC 2115106. PMID 2964450. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2115106. 
  9. ^ Höning S, Sosa M, Hille-Rehfeld A, von Figura K (August 1997). "The 46-kDa mannose 6-phosphate receptor contains multiple binding sites for clathrin adaptors". J. Biol. Chem. 272 (32): 19884–90. doi:10.1074/jbc.272.32.19884. PMID 9242653. 
  10. ^ Puertollano R, Aguilar RC, Gorshkova I, Crouch RJ, Bonifacino JS (June 2001). "Sorting of mannose 6-phosphate receptors mediated by the GGAs". Science 292 (5522): 1712–6. doi:10.1126/science.1060750. PMID 11387475. 
  11. ^ Zhu Y, Doray B, Poussu A, Lehto VP, Kornfeld S (June 2001). "Binding of GGA2 to the lysosomal enzyme sorting motif of the mannose 6-phosphate receptor". Science 292 (5522): 1716–8. doi:10.1126/science.1060896. PMID 11387476. 
  12. ^ a b c Waguri S, Dewitte F, Le Borgne R, Rouillé Y, Uchiyama Y, Dubremetz JF, Hoflack B (January 2003). "Visualization of TGN to endosome trafficking through fluorescently labeled MPR and AP-1 in living cells". Mol. Biol. Cell 14 (1): 142–55. doi:10.1091/mbc.E02-06-0338. PMC 140234. PMID 12529433. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=140234. 
  13. ^ Le Borgne R, Hoflack B (April 1997). "Mannose 6-phosphate receptors regulate the formation of clathrin-coated vesicles in the TGN". J. Cell Biol. 137 (2): 335–45. doi:10.1083/jcb.137.2.335. PMC 2139777. PMID 9128246. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2139777. 
  14. ^ Meyer C, Zizioli D, Lausmann S, Eskelinen EL, Hamann J, Saftig P, von Figura K, Schu P (May 2000). "mu1A-adaptin-deficient mice: lethality, loss of AP-1 binding and rerouting of mannose 6-phosphate receptors". EMBO J. 19 (10): 2193–203. doi:10.1093/emboj/19.10.2193. PMC 384363. PMID 10811610. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=384363. 
  15. ^ Arighi CN, Hartnell LM, Aguilar RC, Haft CR, Bonifacino JS (April 2004). "Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor". J. Cell Biol. 165 (1): 123–33. doi:10.1083/jcb.200312055. PMC 2172094. PMID 15078903. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2172094. 
  16. ^ Mallard F, Antony C, Tenza D, Salamero J, Goud B, Johannes L (November 1998). "Direct pathway from early/recycling endosomes to the Golgi apparatus revealed through the study of shiga toxin B-fragment transport". J. Cell Biol. 143 (4): 973–90. doi:10.1083/jcb.143.4.973. PMC 2132951. PMID 9817755. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132951. 
  17. ^ Nichols, B. J., Kenworthy, A. K., Polishchuk, R. S., Lodge, R., Roberts, T. H., Hirschberg, K., Phair, R. D. and Lippincott-Schwartz, J (2001). "Rapid cycling of lipid raft markers between the cell surface and Golgi complex". J. Cell Biol. 153 (3): 529–554. doi:10.1083/jcb.153.3.529. PMC 2190578. PMID 11331304. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2190578. 
  18. ^ Ghosh RN, Mallet WG, Soe TT, McGraw TE, Maxfield FR (August 1998). "An endocytosed TGN38 chimeric protein is delivered to the TGN after trafficking through the endocytic recycling compartment in CHO cells". J. Cell Biol. 142 (4): 923–36. doi:10.1083/jcb.142.4.923. PMC 2132871. PMID 9722606. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132871. 
  19. ^ Borden LA, Einstein R, Gabel CA, Maxfield FR (May 1990). "Acidification-dependent dissociation of endocytosed insulin precedes that of endocytosed proteins bearing the mannose 6-phosphate recognition marker". J. Biol. Chem. 265 (15): 8497–504. PMID 2160460. 
  20. ^ Yamashiro DJ, Maxfield FR (December 1987). "Acidification of morphologically distinct endosomes in mutant and wild-type Chinese hamster ovary cells". J. Cell Biol. 105 (6 Pt 1): 2723–33. doi:10.1083/jcb.105.6.2723. PMC 2114723. PMID 2447098. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2114723. 
  21. ^ Shapiro AD, Riederer MA, Pfeffer SR (April 1993). "Biochemical analysis of rab9, a ras-like GTPase involved in protein transport from late endosomes to the trans Golgi network". J. Biol. Chem. 268 (10): 6925–31. PMID 8463223. 
  22. ^ a b Press B, Feng Y, Hoflack B, Wandinger-Ness A (March 1998). "Mutant Rab7 causes the accumulation of cathepsin D and cation-independent mannose 6-phosphate receptor in an early endocytic compartment". J. Cell Biol. 140 (5): 1075–89. doi:10.1083/jcb.140.5.1075. PMC 2132709. PMID 9490721. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132709. 
  23. ^ Rojas R, van Vlijmen T, Mardones GA, Prabhu Y, Rojas AL, Mohammed S, Heck AJ, Raposo G, van der Sluijs P, Bonifacino JS (November 2008). "Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7". J. Cell Biol. 183 (3): 513–26. doi:10.1083/jcb.200804048. PMC 2575791. PMID 18981234. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2575791. 
  24. ^ Seaman MN, Harbour ME, Tattersall D, Read E, Bright N (July 2009). "Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5". J. Cell. Sci. 122 (Pt 14): 2371–82. doi:10.1242/jcs.048686. PMC 2704877. PMID 19531583. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2704877. 

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