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• W2150019910 endingPage "4457" @default.
• W2150019910 startingPage "4448" @default.
• W2150019910 abstract "Little is known about the molecular mechanism of recycling of intracellular receptors and lipid raft-associated proteins. Here, we have investigated the recycling pathway and internalization mechanism of a transmembrane, lipid raft-associated intracellular prohormone sorting receptor, carboxypeptidase E (CPE). CPE is found in the trans-Golgi network (TGN) and secretory granules of (neuro)endocrine cells. An extracellular domain of the IL2 receptor alpha-subunit (Tac) fused to the transmembrane domain and cytoplasmic tail of CPE (Tac-CPE25) was used as a marker to track recycling of CPE. We show in (neuro)endocrine cells, that upon stimulated secretory granule exocytosis, raft-associated Tac-CPE25 was rapidly internalized from the plasma membrane in a clathrin-independent manner into early endosomes and then transported through the endocytic recycling compartment to the TGN. A yeast two-hybrid screen and in vitro binding assay identified the CPE cytoplasmic tail sequence S472ETLNF477 as an interactor with active small GTPase ADP-ribosylation factor (ARF) 6, but not ARF1. Expression of a dominant negative, inactive ARF6 mutant blocked this recycling. Mutation of residues S472 or E473 to A in the cytoplasmic tail of CPE obliterated its binding to ARF6, and internalization from the plasma membrane of Tac-CPE25 mutated at S472 or E473 was significantly reduced. Thus, CPE recycles back to the TGN by a novel mechanism requiring ARF6 interaction and activity." @default.
• W2150019910 created "2016-06-24" @default.
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• W2150019910 creator A5060117613 @default.
• W2150019910 date "2003-11-01" @default.
• W2150019910 modified "2023-10-14" @default.
• W2150019910 title "Recycling of Raft-associated Prohormone Sorting Receptor Carboxypeptidase E Requires Interaction with ARF6" @default.
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• W2150019910 doi "https://doi.org/10.1091/mbc.e02-11-0758" @default.
• W2150019910 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/266764" @default.
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• W2150019910 hasPublicationYear "2003" @default.
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