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. 1997 Nov 1;327(Pt 3):811–818. doi: 10.1042/bj3270811

The 46 kDa mannose-6-phosphate receptor contains a signal for basolateral sorting within the 19 juxtamembrane cytosolic residues.

R Bresciani 1, K Denzer 1, R Pohlmann 1, K von Figura 1
PMCID: PMC1218861  PMID: 9581560

Abstract

The cytosolic domain of the 46 kDa mannose-6-phosphate receptor (MPR 46) contains a signal that mediates sorting of the receptor and of a reporter protein to the basolateral surface domain of Madin-Darby canine kidney cells. Progressive truncation of the 67 cytosolic residues indicated that the 19 juxtamembrane residues are sufficient for basolateral sorting. Alanine/glycine-scanning mutagenesis identified Glu-11 and Ala-17 as the critical residues between residues 7 and 19. Glu-11 is also of critical importance for the one of the three internalization signals in the cytosolic tail of the receptor [Denzer, Weber, Hille-Rehfeld, von Figura and Pohlmann (1997) Biochem. J. 326, 497-505]. Although overlapping, the signals for basolateral sorting and internalization depend on different residues. The basolateral sorting signal of MPR 46 is distinct from tyrosine- or dileucine-based basolateral sorting signals and also lacks similarity to the few other basolateral signals that do not fall into these two classes.

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Selected References

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  1. Aroeti B., Kosen P. A., Kuntz I. D., Cohen F. E., Mostov K. E. Mutational and secondary structural analysis of the basolateral sorting signal of the polymeric immunoglobulin receptor. J Cell Biol. 1993 Dec;123(5):1149–1160. doi: 10.1083/jcb.123.5.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bremnes B., Madsen T., Gedde-Dahl M., Bakke O. An LI and ML motif in the cytoplasmic tail of the MHC-associated invariant chain mediate rapid internalization. J Cell Sci. 1994 Jul;107(Pt 7):2021–2032. doi: 10.1242/jcs.107.7.2021. [DOI] [PubMed] [Google Scholar]
  3. Brewer C. B., Roth M. G. A single amino acid change in the cytoplasmic domain alters the polarized delivery of influenza virus hemagglutinin. J Cell Biol. 1991 Aug;114(3):413–421. doi: 10.1083/jcb.114.3.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Casanova J. E., Apodaca G., Mostov K. E. An autonomous signal for basolateral sorting in the cytoplasmic domain of the polymeric immunoglobulin receptor. Cell. 1991 Jul 12;66(1):65–75. doi: 10.1016/0092-8674(91)90139-p. [DOI] [PubMed] [Google Scholar]
  5. Chao H. H., Waheed A., Pohlmann R., Hille A., von Figura K. Mannose 6-phosphate receptor dependent secretion of lysosomal enzymes. EMBO J. 1990 Nov;9(11):3507–3513. doi: 10.1002/j.1460-2075.1990.tb07559.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dahms N. M., Lobel P., Kornfeld S. Mannose 6-phosphate receptors and lysosomal enzyme targeting. J Biol Chem. 1989 Jul 25;264(21):12115–12118. [PubMed] [Google Scholar]
  7. Dargemont C., Le Bivic A., Rothenberger S., Iacopetta B., Kühn L. C. The internalization signal and the phosphorylation site of transferrin receptor are distinct from the main basolateral sorting information. EMBO J. 1993 Apr;12(4):1713–1721. doi: 10.1002/j.1460-2075.1993.tb05816.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Denzer K., Weber B., Hille-Rehfeld A., Figura K. V., Pohlmann R. Identification of three internalization sequences in the cytoplasmic tail of the 46 kDa mannose 6-phosphate receptor. Biochem J. 1997 Sep 1;326(Pt 2):497–505. doi: 10.1042/bj3260497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fuller S. D., Bravo R., Simons K. An enzymatic assay reveals that proteins destined for the apical or basolateral domains of an epithelial cell line share the same late Golgi compartments. EMBO J. 1985 Feb;4(2):297–307. doi: 10.1002/j.1460-2075.1985.tb03629.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Geffen I., Fuhrer C., Leitinger B., Weiss M., Huggel K., Griffiths G., Spiess M. Related signals for endocytosis and basolateral sorting of the asialoglycoprotein receptor. J Biol Chem. 1993 Oct 5;268(28):20772–20777. [PubMed] [Google Scholar]
  11. Hille-Rehfeld A. Mannose 6-phosphate receptors in sorting and transport of lysosomal enzymes. Biochim Biophys Acta. 1995 Jul 17;1241(2):177–194. doi: 10.1016/0304-4157(95)00004-b. [DOI] [PubMed] [Google Scholar]
  12. Hunziker W., Fumey C. A di-leucine motif mediates endocytosis and basolateral sorting of macrophage IgG Fc receptors in MDCK cells. EMBO J. 1994 Jul 1;13(13):2963–2969. doi: 10.1002/j.1460-2075.1994.tb06594.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hunziker W., Harter C., Matter K., Mellman I. Basolateral sorting in MDCK cells requires a distinct cytoplasmic domain determinant. Cell. 1991 Sep 6;66(5):907–920. doi: 10.1016/0092-8674(91)90437-4. [DOI] [PubMed] [Google Scholar]
  14. Klumperman J., Fransen J. A., Tager J. M., Ginsel L. A. The cation-independent mannose 6-phosphate receptor is not involved in the polarized secretion of lysosomal alpha-glucosidase from Caco-2 cells. Eur J Cell Biol. 1992 Apr;57(2):147–154. [PubMed] [Google Scholar]
  15. Kornfeld S., Mellman I. The biogenesis of lysosomes. Annu Rev Cell Biol. 1989;5:483–525. doi: 10.1146/annurev.cb.05.110189.002411. [DOI] [PubMed] [Google Scholar]
  16. Lehmann L. E., Eberle W., Krull S., Prill V., Schmidt B., Sander C., von Figura K., Peters C. The internalization signal in the cytoplasmic tail of lysosomal acid phosphatase consists of the hexapeptide PGYRHV. EMBO J. 1992 Dec;11(12):4391–4399. doi: 10.1002/j.1460-2075.1992.tb05539.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Matlin K. S., Simons K. Sorting of an apical plasma membrane glycoprotein occurs before it reaches the cell surface in cultured epithelial cells. J Cell Biol. 1984 Dec;99(6):2131–2139. doi: 10.1083/jcb.99.6.2131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matter K., Hunziker W., Mellman I. Basolateral sorting of LDL receptor in MDCK cells: the cytoplasmic domain contains two tyrosine-dependent targeting determinants. Cell. 1992 Nov 27;71(5):741–753. doi: 10.1016/0092-8674(92)90551-m. [DOI] [PubMed] [Google Scholar]
  19. Mays R. W., Beck K. A., Nelson W. J. Organization and function of the cytoskeleton in polarized epithelial cells: a component of the protein sorting machinery. Curr Opin Cell Biol. 1994 Feb;6(1):16–24. doi: 10.1016/0955-0674(94)90111-2. [DOI] [PubMed] [Google Scholar]
  20. Misek D. E., Bard E., Rodriguez-Boulan E. Biogenesis of epithelial cell polarity: intracellular sorting and vectorial exocytosis of an apical plasma membrane glycoprotein. Cell. 1984 Dec;39(3 Pt 2):537–546. doi: 10.1016/0092-8674(84)90460-4. [DOI] [PubMed] [Google Scholar]
  21. Monlauzeur L., Rajasekaran A., Chao M., Rodriguez-Boulan E., Le Bivic A. A cytoplasmic tyrosine is essential for the basolateral localization of mutants of the human nerve growth factor receptor in Madin-Darby canine kidney cells. J Biol Chem. 1995 May 19;270(20):12219–12225. doi: 10.1074/jbc.270.20.12219. [DOI] [PubMed] [Google Scholar]
  22. Mostov K., Apodaca G., Aroeti B., Okamoto C. Plasma membrane protein sorting in polarized epithelial cells. J Cell Biol. 1992 Feb;116(3):577–583. doi: 10.1083/jcb.116.3.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Odorizzi C. G., Trowbridge I. S., Xue L., Hopkins C. R., Davis C. D., Collawn J. F. Sorting signals in the MHC class II invariant chain cytoplasmic tail and transmembrane region determine trafficking to an endocytic processing compartment. J Cell Biol. 1994 Jul;126(2):317–330. doi: 10.1083/jcb.126.2.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Okamoto C. T., Shia S. P., Bird C., Mostov K. E., Roth M. G. The cytoplasmic domain of the polymeric immunoglobulin receptor contains two internalization signals that are distinct from its basolateral sorting signal. J Biol Chem. 1992 May 15;267(14):9925–9932. [PubMed] [Google Scholar]
  25. Peters C., Braun M., Weber B., Wendland M., Schmidt B., Pohlmann R., Waheed A., von Figura K. Targeting of a lysosomal membrane protein: a tyrosine-containing endocytosis signal in the cytoplasmic tail of lysosomal acid phosphatase is necessary and sufficient for targeting to lysosomes. EMBO J. 1990 Nov;9(11):3497–3506. doi: 10.1002/j.1460-2075.1990.tb07558.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pohlmann R., Boeker M. W., von Figura K. The two mannose 6-phosphate receptors transport distinct complements of lysosomal proteins. J Biol Chem. 1995 Nov 10;270(45):27311–27318. doi: 10.1074/jbc.270.45.27311. [DOI] [PubMed] [Google Scholar]
  27. Prill V., Lehmann L., von Figura K., Peters C. The cytoplasmic tail of lysosomal acid phosphatase contains overlapping but distinct signals for basolateral sorting and rapid internalization in polarized MDCK cells. EMBO J. 1993 May;12(5):2181–2193. doi: 10.1002/j.1460-2075.1993.tb05866.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Prydz K., Brändli A. W., Bomsel M., Simons K. Surface distribution of the mannose 6-phosphate receptors in epithelial Madin-Darby canine kidney cells. J Biol Chem. 1990 Jul 25;265(21):12629–12635. [PubMed] [Google Scholar]
  29. Punnonen E. L., Wilke T., von Figura K., Hille-Rehfeld A. The oligomeric state of 46-kDa mannose 6-phosphate receptor does not change upon intracellular recycling and binding of ligands. Eur J Biochem. 1996 May 1;237(3):809–818. doi: 10.1111/j.1432-1033.1996.0809p.x. [DOI] [PubMed] [Google Scholar]
  30. Rodriguez-Boulan E., Paskiet K. T., Salas P. J., Bard E. Intracellular transport of influenza virus hemagglutinin to the apical surface of Madin-Darby canine kidney cells. J Cell Biol. 1984 Jan;98(1):308–319. doi: 10.1083/jcb.98.1.308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rodriguez-Boulan E., Powell S. K. Polarity of epithelial and neuronal cells. Annu Rev Cell Biol. 1992;8:395–427. doi: 10.1146/annurev.cb.08.110192.002143. [DOI] [PubMed] [Google Scholar]
  32. Scheiffele P., Peränen J., Simons K. N-glycans as apical sorting signals in epithelial cells. Nature. 1995 Nov 2;378(6552):96–98. doi: 10.1038/378096a0. [DOI] [PubMed] [Google Scholar]
  33. Sheikh H., Isacke C. M. A di-hydrophobic Leu-Val motif regulates the basolateral localization of CD44 in polarized Madin-Darby canine kidney epithelial cells. J Biol Chem. 1996 May 24;271(21):12185–12190. doi: 10.1074/jbc.271.21.12185. [DOI] [PubMed] [Google Scholar]
  34. Simons K., Wandinger-Ness A. Polarized sorting in epithelia. Cell. 1990 Jul 27;62(2):207–210. doi: 10.1016/0092-8674(90)90357-k. [DOI] [PubMed] [Google Scholar]
  35. Thomas D. C., Brewer C. B., Roth M. G. Vesicular stomatitis virus glycoprotein contains a dominant cytoplasmic basolateral sorting signal critically dependent upon a tyrosine. J Biol Chem. 1993 Feb 15;268(5):3313–3320. [PubMed] [Google Scholar]
  36. Thomas D. C., Roth M. G. The basolateral targeting signal in the cytoplasmic domain of glycoprotein G from vesicular stomatitis virus resembles a variety of intracellular targeting motifs related by primary sequence but having diverse targeting activities. J Biol Chem. 1994 Jun 3;269(22):15732–15739. [PubMed] [Google Scholar]
  37. Wandinger-Ness A., Bennett M. K., Antony C., Simons K. Distinct transport vesicles mediate the delivery of plasma membrane proteins to the apical and basolateral domains of MDCK cells. J Cell Biol. 1990 Sep;111(3):987–1000. doi: 10.1083/jcb.111.3.987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wendland M., Waheed A., Schmidt B., Hille A., Nagel G., von Figura K., Pohlmann R. Glycosylation of the Mr 46,000 mannose 6-phosphate receptor. Effect on ligand binding, stability, and conformation. J Biol Chem. 1991 Mar 5;266(7):4598–4604. [PubMed] [Google Scholar]
  39. Yokode M., Pathak R. K., Hammer R. E., Brown M. S., Goldstein J. L., Anderson R. G. Cytoplasmic sequence required for basolateral targeting of LDL receptor in livers of transgenic mice. J Cell Biol. 1992 Apr;117(1):39–46. doi: 10.1083/jcb.117.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]

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