Signal-dependent trafficking of β-amyloid precursor protein-transferrin receptor chimeras in Madin-Darby canine kidney cells
Signal-dependent trafficking of β-amyloid precursor protein-transferrin receptor chimeras in Madin-Darby canine kidney cells
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DOI：
10.1074/jbc.273.6.3732
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发表时间：
1998-02-06
影响因子：
4.8
通讯作者：
Trowbridge, IS
中科院分区：
文献类型：
--
作者：
Lai, A;Gibson, A;Trowbridge, IS
我们研究了由β-淀粉样前体蛋白(APP)的胞浆区和人转铁蛋白受体(TR)的跨膜区和外区组成的嵌合分子在Madin-Darby犬肾细胞内的转运。新合成的APP-TR嵌合体通过APP细胞质尾部的酪氨酸依赖的分选信号选择性地靶向于基底外侧表面。APP-TR嵌合体随后从基底侧面迅速内化，相当一部分(类似于20%-30%)被降解。形态研究表明，APP-tR嵌合体从基底外侧表面内化存在于管泡内体分子、多囊泡体内膜和溶酶体中。在直径为60 nm的囊泡中也发现了APP-TR嵌合体，先前的研究表明，这些囊泡可以选择性地将野生型TR输送到基底侧面；这一结果与90%未降解的内化嵌合体被选择性地循环回到基底侧面表面的事实一致。从顶端表面内化的APP-TR嵌合体被选择性地跨细胞传递到基侧表面，强调了基侧分选在内吞途径中对维持极化表型的重要性。Tyr-653是APP胞质区YTSI内化信号的重要元件，在生物合成和内吞途径中需要进行基侧分选。然而，基侧分类的结构特征与内化所需的结构特征不同。
We have investigated the intracellular trafficking of a chimeric molecule consisting of the cytoplasmic domain of the beta-amyloid precursor protein (APP) and the transmembrane region and external domain of the human transferrin receptor (TR) in Madin-Darby canine kidney cells. Newly synthesized APP-TR chimeras are selectively targeted to the basolateral surface by a tyrosine-dependent sorting signal in the APP cytoplasmic tail. APP-TR chimeras are then rapidly internalized from the basolateral surface and a significant fraction (similar to 20-30%) are degraded. Morphological studies show that APP-TR chimeras internalized from the basolateral surface are found in tubulo-vesicular endosomal elements, internal membranes of multivesicular bodies, and lysosomes. APP-TR chimeras are also found in 60-nm diameter vesicles previously shown to selectively deliver wild-type TR to the basolateral surface; this result is consistent with the fact that 90% of internalized chimeras that are not degraded are selectively recycled back to the basolateral surface. APP-TR chimeras internalized from the apical surface are selectively transcytosed to the basolateral surface underscoring the importance of basolateral sorting in the endocytic pathway for maintaining the polarized phenotype. Tyr-653, an important element of the YTSI internalization signal in the APP cytoplasmic domain, is required for basolateral sorting in the biosynthetic and endocytic pathways. However, the structural features for basolateral sorting differ from those required for internalization.