The tyrosine motifs of Lamp 1 and LAP determine their direct and indirect targetting to lysosomes.
The tyrosine motifs of Lamp 1 and LAP determine their direct and indirect targetting to lysosomes.
复制标题
Lamp 1 和 LAP 的酪氨酸基序决定了它们对溶酶体的直接和间接靶向。
作者：
S. Obermüller;Christina Kiecke;K. von Figura;S. Höning
LAMP 1和溶酶体酸性磷酸酶(LAP)是溶酶体膜蛋白，它们的短胞浆尾中含有基于酪氨酸的分选基序。LAMP 1从跨高尔基网络(TGN)通过内体直接传递到绕过质膜的溶酶体，而LAP间接传递到溶酶体，并在内体和质膜之间循环，然后传递到溶酶体。通过分析LAP和LAMP 1的细胞质尾巴或部分细胞质尾巴互换的截短形式的LAP和嵌合体，我们能够证明LAP的YRHV酪氨酸基序是调节内体和质膜之间循环的必要条件和充分条件。当与LAP和Lamp 1细胞质尾部对应的多肽以及这些尾部的嵌合或突变形式的AP1和AP2体外结合时，我们发现AP2与LAP和Lamp-1衍生的多肽结合，而AP1仅与含有Lamp 1的YQTI酪氨酸基序的多肽结合。酪氨酸基序的+2和+3残基对接头的差异结合是关键的。LAP中这些残基(-HV)被替换为LAMP 1(-TI)的残基被直接运送到溶酶体，而携带LAMP 1尾部的嵌合体获得了回收能力，其中残基+2和+3替换了LAP(-HV)的残基。总之，酪氨酸基序的+2和+3残基决定了LAMP 1和LAP在内体中的分类，介导了直接或间接的溶酶体途径。
Lamp 1 and lysosomal acid phosphatase (LAP) are lysosomal membrane proteins that harbour a tyrosine-based sorting motif within their short cytoplasmic tails. Lamp 1 is delivered from the trans-Golgi network (TGN) via endosomes directly to lysosomes bypassing the plasma membrane, whereas LAP is indirectly transported to lysosomes and recycles between endosomes and the plasma membrane before being delivered to lysosomes. By analysing truncated forms of LAP and chimeras in which the cytoplasmic tail or part of the cytoplasmic tails of LAP and Lamp 1 were exchanged, we were able to show that the YRHV tyrosine motif of LAP is necessary and sufficient to mediate recycling between endosomes and the plasma membrane. When peptides corresponding to the cytoplasmic tails of LAP and Lamp 1 and chimeric or mutant forms of these tails were assayed for in vitro binding of AP1 and AP2, we found that AP2 bound to LAP- and Lamp-1-derived peptides, whereas AP1 bound only to peptides containing the YQTI tyrosine motif of Lamp 1. Residues +2 and +3 of the tyrosine motif were critical for the differential binding of adaptors. LAP in which these residues (-HV) were substituted for those of Lamp 1 (-TI) was transported directly to lysosomes, whereas a chimera carrying the Lamp 1 tail in which residues +2 and +3 were substituted for those of LAP (-HV) gained the ability to recycle. In conclusion, the residues +2 and +3 of the tyrosine motifs determine the sorting of Lamp 1 and LAP in endosomes, mediating either the direct or the indirect pathway to lysosomes.
影响因子：
16
作者：
Dell'Angelica, EC;Shotelersuk, V;Bonifacino, JS
通讯作者：
Bonifacino, JS
溶酶体相关膜蛋白 (LAMP) 对间接溶酶体靶向途径的利用很大程度上受其 GYXXphi 靶向信号的 C 端残基影响。
影响因子：
4
作者：
Gough,NR;Zweifel,ME;Martinez-Augustin,O;Aguilar,RC;Bonifacino,JS;Fambrough,DM
通讯作者：
Fambrough,DM