Roles for Trafficking and O-Linked Glycosylation in the Turnover of Model Cell Surface Proteins |
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Authors: | Darya Karabasheva Nelson B. Cole Julie G. Donaldson |
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Affiliation: | From the Cell Biology and Physiology Center, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 |
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Abstract: | Proteins targeted to the plasma membrane (PM) of cells are degraded at different rates. Sorting motifs contained within the cytoplasmic domains of transmembrane proteins, post-translational modifications (e.g. ubiquitination), and assembly into multiprotein or protein-lipid complexes all may affect the efficiency of endocytosis and recycling and influence the delivery to degradative compartments. Using the SNAP-tag labeling system, we examined the turnover of a model PM protein, the α chain of the interleukin-2 receptor (Tac). The surface lifetimes of SNAP-Tac fusions were influenced by their mode of entry into cells (clathrin-dependent versus clathrin-independent), their orientation in the PM (transmembrane versus glycosylphosphatidylinositol-anchored), and ubiquitination in their cytosolic domains. In addition, shedding of SNAP-Tac into the medium was greatly influenced by its O-linked glycosylation status. For a number of PM proteins, delivery to lysosomes and ectodomain shedding represent distinct parallel mechanisms to determine protein half-life. |
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Keywords: | Endocytosis Lysosome Plasma Membrane Shedding Trafficking |
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