Caspase-1 regulates cellular trafficking via cleavage of the Rab7 adaptor protein RILP.

Caspase-1 regulates cellular trafficking via cleavage of the Rab7 adaptor protein RILP.
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DOI:
10.1016/j.bbrc.2018.08.013
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发表时间:
2018-09-18
影响因子:
3.1
通讯作者:
Wozniak AL
Wozniak AL
中科院分区:
生物学4区
文献类型:
--
作者:
Adams A;Weinman SA;Wozniak AL

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细胞内运输是一个严格调控的细胞过程,部分由Rab GTP酶及其相应的效应蛋白介导。病毒已经进化出了劫持这些过程以促进其生命周期的机制。在这里,我们描述了一种机制,通过这种机制,Rab 7衔接蛋白,RILP(Rab相互作用溶酶体蛋白)的裂解是由病毒感染诱导的。我们的报告,RILP是直接裂解的caspase-1,我们已经确定了一个新的caspase-1的识别位点在天冬氨酸75 RILP序列内。在D 75处的丙氨酸取代阻断胱天蛋白酶-1介导的RILP切割。全长RILP定位于核周区域附近的紧密囊泡结构中,而RILP的裂解形式重新分布在整个细胞质中。然而,单独的切割不足以将RILP重新定位到细胞外周,并且重新定位需要靠近胱天蛋白酶-1识别位点的特异性磷酸化事件。切割和磷酸化的组合都需要从动力蛋白组分p150 Glued释放和CD 63 +ve细胞内囊泡的再分布。
Intracellular trafficking is a tightly regulated cellular process, mediated in part by Rab GTPases and their corresponding effector proteins. Viruses have evolved mechanisms to hijack these processes to promote their lifecycles. Here we describe a mechanism by which cleavage of the Rab7 adaptor protein, RILP (Rab interacting lysosomal protein) is induced by viral infection. We report that RILP is directly cleaved by caspase-1 and we have identified a novel caspase-1 recognition site at aspartic acid 75 within the RILP sequence. Alanine substitution at D75 blocks caspase-1-mediated RILP cleavage. Full-length RILP localizes in a tight vesicular structure near the perinuclear region while the cleaved form of RILP re-distributes throughout the cytoplasm. However, cleavage alone was insufficient to re-localize RILP to the cellular periphery and re-localization required specific phosphorylation events near the caspase-1 recognition site. The combination of cleavage and phosphorylation were both needed for release from the dynein component p150Glued and redistribution of CD63+ve intracellular vesicles.
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