Publication type: Article in scientific journal
Type of review: Peer review (publication)
Title: Characterization of the endosomal sorting signal of the cation-dependent mannose 6-phosphate receptor
Authors: Nair, Prashant
Schaub, Beat E
Rohrer, Jack
DOI: 10.1074/jbc.M300174200
Published in: Journal of Biological Chemistry
Volume(Issue): 278
Issue: 27
Page(s): 24753
Pages to: 24758
Issue Date: 4-Jul-2003
Publisher / Ed. Institution: American Society for Biochemistry and Molecular Biology
ISSN: 1083-351X
Language: English
Subject (DDC): 571: Physiology and related subjects
572: Biochemistry
Abstract: Intracellular cycling of the cation-dependent mannose 6-phosphate receptor (CD-MPR) between different compartments is directed by signals localized in its cytoplasmic tail. A di-aromatic motif (Phe18-Trp19 with Trp19 as the key residue) in its cytoplasmic tail is required for the sorting of the receptor from late endosomes back to the Golgi apparatus. However, the cation-independent mannose 6-phosphate receptor (CI-MPR) lacks such a di-aromatic motif. Therefore the ability of amino acids other than aromatic residues to replace Trp19 in the CD-MPR cytoplasmic tail was tested. Mutant constructs with bulky hydrophobic residues (valine, isoleucine, or leucine) instead of Trp19 exhibited 30-60% decreases in binding to the tail interacting protein of 47 kDa (Tip47), a protein mediating this transport step, and partially prevented receptor delivery to lysosomes. Decreasing hydrophobicity of residues at position 19 resulted in further impairment of Tip47 binding and an increase of receptor accumulation in lysosomes. Intriguingly, mutants mislocalized to lysosomes did not completely co-localize with a lysosomal membrane protein, which might suggest the presence of subdomains within lysosomes. These data indicate that sorting of the CD-MPR in late endosomes requires a distinct di-aromatic motif with only limited possibilities for variations, in contrast to the CI-MPR, which seems to require a putative loop (Pro49-Pro-Ala-Pro-Arg-Pro-Gly55) along with additional hydrophobic residues in the cytoplasmic tail. This raises the possibility of two separate binding sites on Tip47 because both receptors require binding to Tip47 for endosomal sorting.
URI: https://digitalcollection.zhaw.ch/handle/11475/6795
Fulltext version: Published version
License (according to publishing contract): Licence according to publishing contract
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:Publikationen Life Sciences und Facility Management

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Nair, P., Schaub, B. E., & Rohrer, J. (2003). Characterization of the endosomal sorting signal of the cation-dependent mannose 6-phosphate receptor. Journal of Biological Chemistry, 278(27), 24753–24758. https://doi.org/10.1074/jbc.M300174200
Nair, P., Schaub, B.E. and Rohrer, J. (2003) ‘Characterization of the endosomal sorting signal of the cation-dependent mannose 6-phosphate receptor’, Journal of Biological Chemistry, 278(27), pp. 24753–24758. Available at: https://doi.org/10.1074/jbc.M300174200.
P. Nair, B. E. Schaub, and J. Rohrer, “Characterization of the endosomal sorting signal of the cation-dependent mannose 6-phosphate receptor,” Journal of Biological Chemistry, vol. 278, no. 27, pp. 24753–24758, Jul. 2003, doi: 10.1074/jbc.M300174200.
NAIR, Prashant, Beat E SCHAUB und Jack ROHRER, 2003. Characterization of the endosomal sorting signal of the cation-dependent mannose 6-phosphate receptor. Journal of Biological Chemistry. 4 Juli 2003. Bd. 278, Nr. 27, S. 24753–24758. DOI 10.1074/jbc.M300174200
Nair, Prashant, Beat E Schaub, and Jack Rohrer. 2003. “Characterization of the Endosomal Sorting Signal of the Cation-Dependent Mannose 6-Phosphate Receptor.” Journal of Biological Chemistry 278 (27): 24753–58. https://doi.org/10.1074/jbc.M300174200.
Nair, Prashant, et al. “Characterization of the Endosomal Sorting Signal of the Cation-Dependent Mannose 6-Phosphate Receptor.” Journal of Biological Chemistry, vol. 278, no. 27, July 2003, pp. 24753–58, https://doi.org/10.1074/jbc.M300174200.


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