Centralspindlin Recruits ALIX to the Midbody during Cytokinetic Abscission in Drosophila via a Mechanism Analogous to Virus Budding
Centralspindlin Recruits ALIX to the Midbody during Cytokinetic Abscission in Drosophila via a Mechanism Analogous to Virus Budding
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DOI：
10.1016/j.cub.2019.09.025
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发表时间：
2019-10-21
期刊：
影响因子：
9.2
通讯作者：
Haglund, Kaisa
中科院分区：
文献类型：
--
作者：
Lie-Jensen, Anette;Ivanauskiene, Kristina;Haglund, Kaisa
脱落是胞质分裂的最后一步，它将连接两个子细胞的细胞间桥切开[1-6]。支架蛋白阿利克斯是解离机制的核心组分，在ESCRT-III的中间体募集中具有进化上保守的作用[7-11]，其介导最终切割[1-5，8-10，12-14]。在哺乳动物细胞中，centralspindlin复合物募集主要的中间体组织者CEP 55，CEP 55直接结合并募集阿利克斯和ESCRT-I [7-9，15-17]，ALIX和ESCRT-I又协同募集ESCRT-III [8，9，18]。然而，CEP 55在黑腹果蝇和其他无脊椎动物中缺失[6，9，19]，并且不知道在没有CEP 55的情况下，如何将释放机制募集到中间体。在这里，我们解决如何果蝇阿利克斯招募到中体。令人惊讶的是，阿利克斯通过其V结构域定位于中间体，独立于募集人阿利克斯的富含脯氨酸区域中的GPPX（3）Y基序[8，9]。我们阐明，centralspindlin组件帕瓦罗蒂（H. s. MKLP 1）与阿利克斯的V-域相互作用，以招募它的中体。具体而言，我们的结果表明，帕瓦罗蒂中的LxxLF基序直接与阿利克斯V结构域中的保守疏水口袋相互作用，其在人阿利克斯中结合病毒蛋白的（L）YPXnL/LxxLF基序[20-28]。因此，我们的研究确定，阿利克斯是由一个类似的机制，在果蝇的分裂过程中，在哺乳动物细胞中的病毒出芽和centralspindlin的祖先的作用，在招聘的分裂机器中体招募。
Abscission, the final step of cytokinesis, cleaves the thin intercellular bridge connecting the two daughter cells [1-6]. The scaffold protein ALIX is a core component of the abscission machinery with an evolutionarily conserved role in midbody recruitment of ESCRT-III [7-11], which mediates the final cut [1-5, 8-10, 12-14]. In mammalian cells, the centralspindlin complex recruits the major midbody organizer CEP55 that directly binds and recruits ALIX and ESCRT-I [7-9, 15-17], which in turn cooperatively recruit ESCRT-III [8, 9, 18]. However, CEP55 is missing in Drosophila melanogaster and other invertebrates [6, 9, 19], and it is unknown how the abscission machinery is recruited to the midbody in the absence of CEP55. Here, we address how Drosophila ALIX is recruited to the midbody. Surprisingly, ALIX localizes to the midbody via its V-domain, independently of the GPPX(3)Y motif in the proline-rich region that recruits human ALIX [8, 9]. We elucidate that the centralspindlin component Pavarotti (H.s.MKLP1) interacts with the V-domain of ALIX to recruit it to the midbody. Specifically, our results indicate that an LxxLF motif in Pavarotti directly interacts with a conserved hydrophobic pocket in the ALIX V-domain, which in human ALIX binds (L)YPXnL/LxxLF motifs of virus proteins [20-28]. Thus, our study identifies that ALIX is recruited by an analogous mechanism during abscission in Drosophila as during virus budding in mammalian cells and an ancestral role for centralspindlin in recruiting the abscission machinery to the midbody.