| Publication type: | Article in scientific journal |
| Type of review: | Peer review (publication) |
| Title: | Proper sorting of the cation-dependent mannose 6-phosphate receptor in endosomes depends on a pair of aromatic amino acids in its cytoplasmic tail |
| Authors: | Schweizer, Anja Kornfeld, Stuart Rohrer, Jack |
| DOI: | 10.1073/pnas.94.26.14471 |
| Published in: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume(Issue): | 94 |
| Issue: | 26 |
| Page(s): | 14471 |
| Pages to: | 14476 |
| Issue Date: | 23-Dec-1997 |
| Publisher / Ed. Institution: | National Academy of Sciences |
| ISSN: | 0027-8424 1091-6490 |
| Language: | English |
| Subject (DDC): | 571: Physiology and related subjects 572: Biochemistry |
| Abstract: | The 67-amino acid cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor (CD-MPR) contains a signal(s) that prevents the receptor from entering lysosomes where it would be degraded. To identify the key residues required for proper endosomal sorting, we analyzed the intracellular distribution of mutant forms of the receptor by Percoll density gradients. A receptor with a Trp19 --> Ala substitution in the cytoplasmic tail was highly missorted to lysosomes whereas receptors with either Phe18 --> Ala or Phe13 --> Ala mutations were partially defective in avoiding transport to lysosomes. Analysis of double and triple mutants confirmed the key role of Trp19 for sorting of the CD-MPR in endosomes, with Phe18, Phe13, and several neighboring residues contributing to this function. The addition of the Phe18-Trp19 motif of the CD-MPR to the cytoplasmic tail of the lysosomal membrane protein Lamp1 was sufficient to partially impair its delivery to lysosomes. Replacing Phe18 and Trp19 with other aromatic amino acids did not impair endosomal sorting of the CD-MPR, indicating that two aromatic residues located at these positions are sufficient to prevent the receptor from trafficking to lysosomes. However, alterations in the spacing of the diaromatic amino acid sequence relative to the transmembrane domain resulted in receptor accumulation in lysosomes. These findings indicate that the endosomal sorting of the CD-MPR depends on the correct presentation of a diaromatic amino acid-containing motif in its cytoplasmic tail. Because a diaromatic amino acid sequence is also present in the cytoplasmic tail of other receptors known to be internalized from the plasma membrane, this feature may prove to be a general determinant for endosomal sorting. |
| URI: | https://digitalcollection.zhaw.ch/handle/11475/6814 |
| Fulltext version: | Published version |
| License (according to publishing contract): | Licence according to publishing contract |
| Departement: | Life Sciences and Facility Management |
| Appears in collections: | Publikationen Life Sciences und Facility Management |
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Schweizer, A., Kornfeld, S., & Rohrer, J. (1997). Proper sorting of the cation-dependent mannose 6-phosphate receptor in endosomes depends on a pair of aromatic amino acids in its cytoplasmic tail. Proceedings of the National Academy of Sciences of the United States of America, 94(26), 14471–14476. https://doi.org/10.1073/pnas.94.26.14471
Schweizer, A., Kornfeld, S. and Rohrer, J. (1997) ‘Proper sorting of the cation-dependent mannose 6-phosphate receptor in endosomes depends on a pair of aromatic amino acids in its cytoplasmic tail’, Proceedings of the National Academy of Sciences of the United States of America, 94(26), pp. 14471–14476. Available at: https://doi.org/10.1073/pnas.94.26.14471.
A. Schweizer, S. Kornfeld, and J. Rohrer, “Proper sorting of the cation-dependent mannose 6-phosphate receptor in endosomes depends on a pair of aromatic amino acids in its cytoplasmic tail,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 26, pp. 14471–14476, Dec. 1997, doi: 10.1073/pnas.94.26.14471.
SCHWEIZER, Anja, Stuart KORNFELD und Jack ROHRER, 1997. Proper sorting of the cation-dependent mannose 6-phosphate receptor in endosomes depends on a pair of aromatic amino acids in its cytoplasmic tail. Proceedings of the National Academy of Sciences of the United States of America. 23 Dezember 1997. Bd. 94, Nr. 26, S. 14471–14476. DOI 10.1073/pnas.94.26.14471
Schweizer, Anja, Stuart Kornfeld, and Jack Rohrer. 1997. “Proper Sorting of the Cation-Dependent Mannose 6-Phosphate Receptor in Endosomes Depends on a Pair of Aromatic Amino Acids in Its Cytoplasmic Tail.” Proceedings of the National Academy of Sciences of the United States of America 94 (26): 14471–76. https://doi.org/10.1073/pnas.94.26.14471.
Schweizer, Anja, et al. “Proper Sorting of the Cation-Dependent Mannose 6-Phosphate Receptor in Endosomes Depends on a Pair of Aromatic Amino Acids in Its Cytoplasmic Tail.” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 26, Dec. 1997, pp. 14471–76, https://doi.org/10.1073/pnas.94.26.14471.
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