期刊
TRAFFIC
卷 11, 期 6, 页码 843-855出版社
WILEY
DOI: 10.1111/j.1600-0854.2010.01056.x
关键词
AP-2; cargo; clathrin; endocytosis; sorting signals
类别
资金
- Wellcome Trust
- Medical Research Council
- MRC [G0701444] Funding Source: UKRI
- Medical Research Council [G0701444] Funding Source: researchfish
Sorting signals for cargo selection into coated vesicles are usually in the form of short linear motifs. Three motifs for clathrin-mediated endocytosis have been identified: YXX, [D/E]XXXL[L/I] and FXNPXY. To search for new endocytic motifs, we made a library of CD8 chimeras with random sequences in their cytoplasmic tails, and used a novel fluorescence-activated cell sorting (FACS)-based assay to select for endocytosed constructs. Out of the five tails that were most efficiently internalized, only one was found to contain a conventional motif. Two contain dileucine-like sequences that appear to be variations on the [D/E]XXXL[L/I] motif. Another contains a novel internalization signal, YXXXN, which is able to function in cells expressing a mutant mu 2 that cannot bind YXX, indicating that it is not a variation on the YXX motif. Similar sequences are present in endogenous proteins, including a functional YXXXN (in addition to a classical YXX) in cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Thus, the repertoire of endocytic motifs is more extensive than the three well-characterized sorting signals.
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