The cation‐independent mannose‐6‐phosphate receptor binds to soluble GPI‐linked proteins via mannose‐6‐phosphate

Green, Paula J.; Ferguson, Michael A. J.; Robinson, Peter; Feizi, Ten

doi:10.1016/0014-5793(95)00050-j

Cited by 8 publications

(4 citation statements)

References 50 publications

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“…Using gel filtration chromatography, some PAS-stained and Con A-reactive molecules were isolated from the sample in the void and some in the included volume. This result confirmed the findings of previous studies on the cell surface antigens of different Leishmania species suggesting that these cellsurface antigens were in glycoconjugate structure like gp63 [2,3,11,21,22,36]. In these studies gp63 was Table 1.…”

Section: Discussionsupporting

confidence: 95%

A preliminary approach to the separation of Leishmania cell‐surface antigens

Aksoy¹,

Özbilge²,

Keleş

et al. 2004

J of Separation Science

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The purpose of the current study was to characterize Leishmania cell-surface antigens by two different methods established for the purification of glycoproteins and proteins, and to point out a useful approach to define their size and mass heterogeneity. L. tropica parasites were initially isolated from patients with active cutaneous leishmaniasis and were then cultured in vitro. The parasite-cell layer was solubilised with 6 M guanidinium chloride (GuHCl) and subsequently prepared for the purification procedure. The methods used in this work were gel filtration chromatography and isopycnic density-gradient centrifugation. Because of the presence of a substantial amount of non-specific proteins in the culture medium, these methods were not effective alone in distinguishing these antigens. However, a good idea of their N-glycosylated structures could be obtained by using Periodic acid-Schiffs (PAS) and Con A lectin, and also size and mass heterogeneity. A combination of these methods effected a clear separation of the antigens. Amino acid analysis of the purified antigens was performed to positively identify them as well-known Leishmania cell-surface antigen gene products. The results confirmed the presence of more than one cell-surface antigen on the Leishmania parasite and the combination of gel chromatography and density-gradient centrifugation could be useful for their isolation.

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Section: Discussionsupporting

confidence: 95%

A preliminary approach to the separation of Leishmania cell‐surface antigens

Aksoy¹,

Özbilge²,

Keleş

et al. 2004

J of Separation Science

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“…This could be due to the ability of the CI-MPR to rescue the phenotype by targeting GlcNAc-covered enzymes to the lysosome. Another possibility relates to a report that the CI-MPR interacts with GPI-linked molecules, which is dependent upon a Man-6-P diester rather than the inositol 1,2-cyclic phosphate group (51). This interaction with the CI-MPR was speculated to influence the clustering and subsequent transmembrane signaling of GPI-linked molecules (51).…”

Section: Discussionmentioning

confidence: 99%

“…Another possibility relates to a report that the CI-MPR interacts with GPI-linked molecules, which is dependent upon a Man-6-P diester rather than the inositol 1,2-cyclic phosphate group (51). This interaction with the CI-MPR was speculated to influence the clustering and subsequent transmembrane signaling of GPI-linked molecules (51). The GPI portion of mammalian GPI-linked proteins is quite variable and contains several types of diesters including Man-6-P-GlcNAc (52) and mannose 2-phosphate diesters (53).…”

Section: Discussionmentioning

confidence: 99%

Domain 5 of the Cation-Independent Mannose 6-Phosphate Receptor Preferentially Binds Phosphodiesters (Mannose 6-Phosphate N-Acetylglucosamine Ester)

et al. 2007

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The 300 kDa cation-independent mannose 6-phosphate receptor (CI-MPR) and the 46 kDa cation-dependent MPR (CD-MPR) are key components of the lysosomal enzyme targeting system that bind newly synthesized mannose 6-phosphate (Man-6-P)-containing acid hydrolases and divert them from the secretory pathway. Previous studies have mapped two high-affinity Man-6-P binding sites of the CI-MPR to domains 1-3 and 9 and one low-affinity site to domain 5 within its 15-domain extracytoplasmic region. A structure-based sequence alignment predicts that domain 5 contains the four conserved residues (Gln, Arg, Glu, Tyr) identified as essential for Man-6-P binding by the CD-MPR and domains 1-3 and 9 of the CI-MPR. Here we show by surface plasmon resonance (SPR) analyses of constructs containing single amino acid substitutions that these conserved residues (Gln-644, Arg-687, Glu-709, Tyr-714) are critical for carbohydrate recognition by domain 5. Furthermore, the N-glycosylation site at position 711 of domain 5, which is predicted to be located near the binding pocket, has no influence on the carbohydrate binding affinity. Endogenous ligands for the MPRs that contain solely phosphomonoesters (Man-6-P) or phosphodiesters (mannose 6-phosphate N-acetylglucosamine ester, Man-P-GlcNAc) were generated by treating the lysosomal enzyme acid alpha-glucosidase (GAA) with recombinant GlcNAc-phosphotransferase and uncovering enzyme (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase). SPR analyses using these modified GAAs demonstrate that, unlike the CD-MPR or domain 9 of the CI-MPR, domain 5 exhibits a 14-18-fold higher affinity for Man-P-GlcNAc than Man-6-P, implicating this region of the receptor in targeting phosphodiester-containing lysosomal enzymes to the lysosome.

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“…Internalization must then occur via bulk membrane endocytosis, which is very slow compared to targeted internalization, or through extracellular interaction with internalization chaperones, which themselves can be effectively internalized. A candidate chaperone would be the mannose- 6-phosphate receptor that apparently can bind the mannose-6-phosphate group in the GPI-anchor (379). Glucose transporters have been reported to be associated with clathrin-coated pits (380,381), with caveolae (382), or with none of these structures (383).…”

Section: Endocytosis Via Caveolaementioning

confidence: 99%

Generation, Translocation, and Presentation of MHC Class I-Restricted Peptides

Heemels¹

1995

Annual Review of Biochemistry

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C o p y r i g h t 0 A P M I S 1 9 9 8Al%WUSl I S S N 0 9 0 3 -4 6 5 x I S B N 8 7-1 6 -I 6 3 3 0 -3 Journey beyond immunology. Regulation of receptor internalization by major histocompatibility complex class I (MHC-I) and effect of peptides derived from MHC-I Chapter 1 substrate inhibition, as i) the peptide was not phosphorylated despite the presence of two tyrosines at the carboxylterminus, and ii) a recombinant, truncated form of the insulin receptor, consisting of only the tyrosine kinase domain of the intracellular part of the P-chain, was not affected by the peptide. The latter observation shows that the effect must occur through binding to the extracellular portion of the receptor. An interesting and novel observation was made using the peptide to inhibit full-length insulin receptor, in that this inhibited receptor could only become phosphorylated by the isolated tyrosine kinase domain if insulin was present. In other words, the fill-length receptor must undergo a ligand-induced conformational change resulting in exposure of phosphorylatable amino acid residues. Biologically sensible, of course, but difficult to prove without the selective, inhibitory activity of the MHC-I peptides.Covalent cross-linking of insulin has also been used to show that intermolecular phosphorylation does not activate the receptor tyrosine kinase (143), although some phosphorylation in trans may occur. In contrast, the EGF receptor is capable of transphosphorylation (144). A mutant insulin receptor (Phe382-Val) with normal insulin binding does not become kinase active after insulin stimulation, but is able to become phosphorylated by insulin-stimulated wild-type receptor, and apparently then becomes kinase active (145). This peculiar mutation in the a-subunit of the receptor must therefore disallow an insulin-triggered conformational change resulting in kinase activation, yet exhibit a conformation that allows phosphorylation of tyrosines and subsequent kinase activation (a rather convoluted hypothesis!). As we did not determine which residues of the MHC-I pep-J. Reiland and M. Edidin. Chemical cross-linking detects association of insulin receptors with four different class I human leukocyte antigen molecules on cell surfaces. Diabetes 42,619-25 (1993) T. Liegler, J. Alexander, P. Cresswell, I. Goldhe, and R. S. Goodenow. An analysis of insulin recptor expression and binding on MHC class I positive and negative human lymphoblastoid cells.

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The cation‐independent mannose‐6‐phosphate receptor binds to soluble GPI‐linked proteins via mannose‐6‐phosphate

Cited by 8 publications

References 50 publications

A preliminary approach to the separation of Leishmania cell‐surface antigens

A preliminary approach to the separation of Leishmania cell‐surface antigens

Domain 5 of the Cation-Independent Mannose 6-Phosphate Receptor Preferentially Binds Phosphodiesters (Mannose 6-Phosphate N-Acetylglucosamine Ester)

Generation, Translocation, and Presentation of MHC Class I-Restricted Peptides

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