ArticleProceedings of the National Academy of Sciences of the United States of America1997
Proper sorting of the cation-dependent mannose 6-phosphate receptor in endosomes depends on a pair of aromatic amino acids in its cytoplasmic tail.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 87 citations in OpenAlex.
- M6PR- and EphB4-Rich Exosomes Secreted by Serglycin-Overexpressing Esophageal Cancer Cells Promote Cancer Progression.International journal of biological sciences · 2023Article
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- Analysis of the SNARE Stx8 recycling reveals that the retromer-sorting motif has undergone evolutionary divergence.PLoS genetics · 2021Article
- Lysosome biogenesis in health and disease.Journal of neurochemistry · 2019Review
- Mechanisms and concepts paving the way towards a complete transport cycle of plant vacuolar sorting receptors.The Plant cell · 2012Review
- Article
- A threonine-based targeting signal in the human CD1d cytoplasmic tail controls its functional expression.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- Down syndrome fibroblast model of Alzheimer-related endosome pathology: accelerated endocytosis promotes late endocytic defects.The American journal of pathology · 2008Article
- The palmitoyltransferase of the cation-dependent mannose 6-phosphate receptor cycles between the plasma membrane and endosomes.Molecular biology of the cell · 2004Article
- Targeting of the human immunodeficiency virus type 1 envelope to the trans-Golgi network through binding to TIP47 is required for env incorporation into virions and infectivity.Journal of virology · 2003Article
- Visualization of TGN to endosome trafficking through fluorescently labeled MPR and AP-1 in living cells.Molecular biology of the cell · 2003Article
- Role of LAMP-2 in lysosome biogenesis and autophagy.Molecular biology of the cell · 2002Article
- Multiple endocytic signals in the C-terminal tail of the cystic fibrosis transmembrane conductance regulator.The Biochemical journal · 2001Article
- Essential role played by the C-terminal domain of glycoprotein I in envelopment of varicella-zoster virus in the trans-Golgi network: interactions of glycoproteins with tegument.Journal of virology · 2001Article
- Rapid transport of internalized P-selectin to late endosomes and the TGN: roles in regulating cell surface expression and recycling to secretory granules.The Journal of cell biology · 2000Article
- Recognition of the 300-kDa mannose 6-phosphate receptor cytoplasmic domain by 47-kDa tail-interacting protein.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
- The PC6B cytoplasmic domain contains two acidic clusters that direct sorting to distinct trans-Golgi network/endosomal compartments.Molecular biology of the cell · 2000Article
- Role for dynamin in late endosome dynamics and trafficking of the cation-independent mannose 6-phosphate receptor.Molecular biology of the cell · 2000Article
- A membrane coat complex essential for endosome-to-Golgi retrograde transport in yeast.The Journal of cell biology · 1998Article
- An atypical sorting determinant in the cytoplasmic domain of P-selectin mediates endosomal sorting.Molecular biology of the cell · 1998Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
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.
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