Microtubule-dependent endosomal sorting of clathrin-independent cargo by Hook1.

Microtubule-dependent endosomal sorting of clathrin-independent cargo by Hook1.
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DOI:
10.1083/jcb.201208172
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发表时间:
2013-04-15
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Donaldson JG
Donaldson JG
中科院分区:
其他
文献类型:
--
作者:
Maldonado-Báez L;Cole NB;Krämer H;Donaldson JG

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Hook1是一种微管和货物拴系蛋白,对于从EEA1+内体分离的不依赖于笼蛋白的货物的分选和促进它们的回收是重要的。许多质膜蛋白通过网状蛋白非依赖性内吞作用(CIE)非选择性地进入细胞。在这里,我们提出的证据表明,三种CIE货运蛋白-CD44、CD98和CD147的细胞质序列负责将这些蛋白快速分选到远离与早期内体抗原1(EEA1)相关的内小体的内小管中。我们发现,Hook1,一种微管和货物拴系蛋白,识别CD147的细胞质尾巴,帮助将其和CD98分类成与循环相关的Rab22a依赖的小管。耗尽细胞中的Hook1改变了CD44、CD98和CD147向EEA1隔间的运输,并损害了CD98返回PM的循环相反,另一种CIE货物蛋白,主要组织相容性复合体I类,通常运输到EEA1间隔,没有受到Hook1耗尽的影响。Hook1的缺失也导致了细胞扩散的抑制,暗示了Hook1对特定的CIE货物蛋白从散装膜上分离并返回PM的作用
Hook1, a microtubule and cargo tethering protein, is important for the sorting of clathrin-independent cargoes away from EEA1+ endosomes and promotes their recycling. Many plasma membrane (PM) proteins enter cells nonselectively through clathrin-independent endocytosis (CIE). Here, we present evidence that cytoplasmic sequences in three CIE cargo proteins—CD44, CD98, and CD147—were responsible for the rapid sorting of these proteins into endosomal tubules away from endosomes associated with early endosomal antigen 1 (EEA1). We found that Hook1, a microtubule- and cargo-tethering protein, recognized the cytoplasmic tail of CD147 to help sort it and CD98 into Rab22a-dependent tubules associated with recycling. Depletion of Hook1 from cells altered trafficking of CD44, CD98, and CD147 toward EEA1 compartments and impaired the recycling of CD98 back to the PM. In contrast, another CIE cargo protein, major histocompatibility complex class I, which normally traffics to EEA1 compartments, was not affected by depletion of Hook1. Loss of Hook1 also led to an inhibition of cell spreading, implicating a role for Hook1 sorting of specific CIE cargo proteins away from bulk membrane and back to the PM.
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