Multiple motifs regulate trafficking of the LAMP-like protein p67 in the ancient eukaryote Trypanosoma brucei.
Multiple motifs regulate trafficking of the LAMP-like protein p67 in the ancient eukaryote Trypanosoma brucei.
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多种基序调节古代真核生物布氏锥虫中 LAMP 样蛋白 p67 的运输。
DOI：
10.1111/j.1600-0854.2007.00588.x
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Bangs,JamesD
中科院分区：
文献类型：
--
作者：
Tazeh,NgiiN;Bangs,JamesD
p67 is a lysosome‐associated membrane protein–like lysosomal type I transmembrane glycoprotein in African trypanosomes. The p67 cytoplasmic domain (CD) is both necessary and sufficient for lysosomal targeting in procyclic insect‐stage parasites. The p67CD contains two [DE]XXXL[LI]‐type dileucine motifs, which function as lysosomal targeting signals in mammalian cells. Using a green fluorescent protein fusion to the p67 transmembrane and cytoplasmic domains as a reporter system, we investigated the role of these motifs in lysosomal targeting in procyclic trypanosomes. Pulse–chase turnover studies, steady‐state immunolocalization and quantitative flow cytometry all gave consistent results. Mutagenesis of the membrane‐distal dileucine motif impairs lysosomal trafficking leading to partial appearance of the reporter on the cell surface. Mutagenesis of the membrane‐proximal motif has little effect on proper targeting. Simultaneous mutagenesis of both motifs results in quantitative delivery to the cell surface. Thus, the distal motif plays a dominant role, but both dileucine motifs are necessary for maximal lysosomal targeting. Additional studies suggest that the upstream acidic residues in each motif influence lysosomal targeting and may also affect forward trafficking in the early secretory pathway. These results strongly suggest an evolutionary conservation in lysosomal trafficking mechanisms in the ancient eukaryoteTrypanosoma brucei.
