Role of cytoplasmic domain serines in intracellular trafficking of furin
| Autor: | Florencia B. Schapiro, William G. Mallet, Thwe Thwe Soe, Frederick R. Maxfield |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cytoplasm
animal structures Time Factors Endosome media_common.quotation_subject viruses Recombinant Fusion Proteins Endocytic recycling CHO Cells Endosomes Biology Models Biological symbols.namesake Cricetinae Serine Animals Internalization Molecular Biology Furin media_common Cell Membrane Receptors Interleukin-2 Cell Biology Articles Golgi apparatus Transmembrane protein Cell biology Transport protein Protein Structure Tertiary Transmembrane domain stomatognathic diseases Protein Transport Amino Acid Substitution embryonic structures symbols biology.protein trans-Golgi Network |
| Zdroj: | Molecular biology of the cell. 15(6) |
| ISSN: | 1059-1524 |
| Popis: | Furin is a transmembrane protein that cycles between the plasma membrane, endosomes, and the trans-Golgi network, maintaining a predominant distribution in the latter. It has been shown previously that Tac-furin, a chimeric protein expressing the extracellular and transmembrane domains of the interleukin-2 receptor α chain (Tac) and the cytoplasmic domain of furin, is delivered from the plasma membrane to the TGN through late endosomes, bypassing the endocytic recycling compartment. Tac-furin also recycles in a loop between the TGN and late endosomes. Localization of furin to the TGN is modulated by a six-amino acid acidic cluster that contains two phosphorylatable serines (SDSEED). We investigated the role of these serines in the trafficking of Tac-furin by using a mutant chimera in which the SDS sequence was replaced by the nonphosphorylatable sequence ADA (Tac-furin/ADA). Although the mutant construct is internalized and delivered to the TGN, both the postendocytic trafficking and the steady-state distribution were found to differ from the wild-type. In contrast with Tac-furin, Tac-furin/ADA does not enter late endosomes after being internalized. Instead, it traffics with transferrin to the endocytic recycling compartment, and from there it is delivered to the TGN. As with Tac-furin, Tac-furin/ADA is sorted from the TGN into late endosomes at steady state, but its retrieval from the late endosomes to the TGN is inhibited. These results suggest that serine phosphorylation plays an important role in at least two steps of Tac-furin trafficking, acting as an active sorting signal that mediates the selective sorting of Tac-furin into late endosomes after internalization, as well as its retrieval from late endosomes back to the TGN. |
| Databáze: | OpenAIRE |
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