Basolateral sorting of the coxsackie and adenovirus receptor through interaction of a canonical YXXΦ motif with the clathrin adaptors AP-1A and AP-1B
Basolateral sorting of the coxsackie and adenovirus receptor through interaction of a canonical YXXΦ motif with the clathrin adaptors AP-1A and AP-1B
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DOI：
10.1073/pnas.1117949109
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发表时间：
2012-03-06
影响因子：
11.1
通讯作者：
Rodriguez-Boulan, Enrique
中科院分区：
文献类型：
--
作者：
Carvajal-Gonzalez, Jose Maria;Gravotta, Diego;Rodriguez-Boulan, Enrique
科萨基和腺病毒受体（CAR）在紧密连接处的上皮屏障功能中起关键作用，紧密连接是部分由基于酪氨酸的基底外侧分选信号（318）YNQV（321）引导的定位。已知这种类型的分选基序通过与网格蛋白衔接子AP-2的中亚基（mu 2）相互作用将表面受体路由到网格蛋白介导的内吞作用中，但它们如何引导新的和再循环的基底膜蛋白尚不清楚。在这里，我们表明，YNQV作为一个典型的YXX Phi基序的功能，与Y318和V321所需的正确基底外侧定位和生物合成的CAR排序，并与网格蛋白衔接子AP-1A和AP-1B的介质亚基（mu 1A和mu 1B）中的高度保守的口袋相互作用。敲除实验表明，AP-1A在CAR的生物合成分选中起作用，与AP-1B在该受体的基底外侧再循环中的作用互补。我们的研究说明了两个网格蛋白衔接子如何通过与典型的YXX Phi基序相互作用来指导质膜蛋白的基底外侧贩运。
The coxsackie and adenovirus receptor (CAR) plays key roles in epithelial barrier function at the tight junction, a localization guided in part by a tyrosine-based basolateral sorting signal, (318)YNQV(321). Sorting motifs of this type are known to route surface receptors into clathrin-mediated endocytosis through interaction with the medium subunit (mu 2) of the clathrin adaptor AP-2, but how they guide new and recycling membrane proteins basolaterally is unknown. Here, we show that YNQV functions as a canonical YXX Phi motif, with both Y318 and V321 required for the correct basolateral localization and biosynthetic sorting of CAR, and for interaction with a highly conserved pocket in the medium subunits (mu 1A and mu 1B) of the clathrin adaptors AP-1A and AP-1B. Knock-down experiments demonstrate that AP-1A plays a role in the biosynthetic sorting of CAR, complementary to the role of AP-1B in basolateral recycling of this receptor. Our study illustrates how two clathrin adaptors direct basolateral trafficking of a plasma membrane protein through interaction with a canonical YXX Phi motif.