CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling.
CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling.
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DOI：
10.1091/mbc.e04-11-1014
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发表时间：
2005-05
影响因子：
3.3
通讯作者：
Qing Yan;Wei Sun;P. Kujala;Yasmin Lotfi;T. Vida;A. Bean
中科院分区：
文献类型：
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作者：
Qing Yan;Wei Sun;P. Kujala;Yasmin Lotfi;T. Vida;A. Bean
改变表面受体的数量可以快速调节细胞对细胞外信号的反应。一些受体，如转铁蛋白受体（TfR），组成性内化并再循环至质膜。其他受体，如表皮生长因子受体（EGFR），在配体结合后内化，然后最终在溶酶体中降解。路由内化受体到不同的目的地表明，不同的分子机制可能会指导他们的运动。在这里，我们报告说，内体相关蛋白小时是一个亚基的蛋白复合物含有辅肌动蛋白-4，BERP，和肌球蛋白V是必要的有效的TfR回收，但不是EGFR降解。hrs/辅肌动蛋白-4/BERP/肌球蛋白V（CART [细胞因子相关的再循环或转运]）复合物以线性方式组装，并且中断任何成员与其相邻成员的结合产生转铁蛋白再循环速率的抑制。破坏CART复合物导致受体分流到涉及再循环内体的较慢再循环途径。新的CART复合物可能提供了一个组成性再循环质膜受体的快速再循环的肌动蛋白依赖性的分子机制。
Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The hrs/actinin-4/BERP/myosin V (CART [cytoskeleton-associated recycling or transport]) complex assembles in a linear manner and interrupting binding of any member to its neighbor produces an inhibition of transferrin recycling rate. Disrupting the CART complex results in shunting receptors to a slower recycling pathway that involves the recycling endosome. The novel CART complex may provide a molecular mechanism for the actin-dependence of rapid recycling of constitutively recycled plasma membrane receptors.