Polarized Traffic of LRP1 Involves AP1B and SNX17 Operating on Y- dependent Sorting Motifs in Different Pathways
Polarized Traffic of LRP1 Involves AP1B and SNX17 Operating on Y- dependent Sorting Motifs in Different Pathways
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DOI：
10.1091/mbc.e08-08-0805
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发表时间：
2009-01-01
影响因子：
3.3
通讯作者：
Marzolo, Maria-Paz
中科院分区：
文献类型：
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作者：
Donoso, Maribel;Cancino, Jorge;Marzolo, Maria-Paz
低密度脂蛋白受体相关蛋白1（LRP 1）是一种内吞再循环受体，具有两个基于细胞质酪氨酸的基底外侧分选信号。在这里，我们表明，在生物合成贩运LRP 1使用AP 1B接头复合物从后TGN再循环内体（RE）移动到基底外侧膜。然后，它从基底外侧分选内体（BSE）向基底外侧延伸，涉及通过分选连接蛋白17（SNX 17）的识别。在生物合成途径中，来自近端NPXY的Y-29而不是N-26指导来自TGN的LRP 1基底外侧分选。一个N（26）A突变体揭示了SNX 17识别的NPXY基序是受体退出BSE所必需的。内吞Y（63）ATL（66）基序也与额外的内吞基序（LL 86，87）一起，通过阻止LRP 1进入胞吞顶端途径，在基底外侧再循环中发挥作用。所有这些分类信息在海马神经元中的作用类似于介导LRP 1体树突分布，而不管神经元中是否存在AP 1B。LRP 1基底外侧分布的结果，然后从空间和时间的隔离步骤介导的识别不同的酪氨酸基序。我们还证明了SNX 17在基底外侧/体树突循环中的一种新功能，该功能来自于与AP 1B内体不同的隔室。
Low-density lipoprotein receptor-related protein 1 (LRP1) is an endocytic recycling receptor with two cytoplasmic tyrosine-based basolateral sorting signals. Here we show that during biosynthetic trafficking LRP1 uses AP1B adaptor complex to move from a post-TGN recycling endosome (RE) to the basolateral membrane. Then it recycles basolaterally from the basolateral sorting endosome (BSE) involving recognition by sorting nexin 17 (SNX17). In the biosynthetic pathway, Y-29 but not N-26 from a proximal NPXY directs LRP1 basolateral sorting from the TGN. A N(26)A mutant revealed that this NPXY motif recognized by SNX17 is required for the receptor's exit from BSE. An endocytic Y(63)ATL(66) motif also functions in basolateral recycling, in concert with an additional endocytic motif (LL86,87), by preventing LRP1 entry into the transcytotic apical pathway. All this sorting information operates similarly in hippocampal neurons to mediate LRP1 somatodendritic distribution regardless of the absence of AP1B in neurons. LRP1 basolateral distribution results then from spatially and temporally segregation steps mediated by recognition of distinct tyrosine-based motifs. We also demonstrate a novel function of SNX17 in basolateral/somatodendritic recycling from a different compartment than AP1B endosomes.