Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release
Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release
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DOI：
10.1073/pnas.0802008105
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发表时间：
2008-07-29
影响因子：
11.1
通讯作者：
Martin-Serrano, Juan
中科院分区：
文献类型：
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作者：
Carlton, Jez G.;Agromayor, Monica;Martin-Serrano, Juan
ESCRT 机制在拓扑等效的膜裂变事件中发挥作用，即多泡体形成、胞质分裂的末期和 HIV-1 释放。在这里，我们证明 ESCRT-III 结合蛋白 Alix 通过进化保守的肽结合 Cep55 被招募到分裂细胞的中体。 Cep55/Alix/ESCRT-III 相互作用的破坏会导致异常中间体的形成和细胞分裂失败，证明这些蛋白质在中间体形态和细胞分裂中发挥重要作用。我们还表明，Alix 的 C 末端编码多聚化活性，这对于 Alix 依赖性 HIV-1 释放以及与 Tsg 101 相互作用的功能至关重要。最后，我们证明 Chmp4b 和 Chmp4c 的过度表达会差异性地抑制 HIV-1 释放和胞质分裂，这表明哺乳动物 E 类 VPS 途径中基因扩展的可能原因。
The ESCRT machinery functions in topologically equivalent membrane fission events, namely multivesicular body formation, the terminal stages of cytokinesis and HIV-1 release. Here, we show that the ESCRT-III-binding protein Alix is recruited to the midbody of dividing cells through binding Cep55 via an evolutionarily conserved peptide. Disruption of Cep55/Alix/ESCRT-III interactions causes formation of aberrant midbodies and cytokinetic failure, demonstrating an essential role for these proteins in midbody morphology and cell division. We also show that the C terminus of Alix encodes a multimerization activity that is essential for its function in Alix-dependent HIV-1 release and for interaction with Tsg 101. Last, we demonstrate that overexpression of Chmp4b and Chmp4c differentially inhibits HIV-1 release and cytokinesis, suggesting possible reasons for gene expansion within the mammalian Class E VPS pathway.