VezA/vezatin 有助于 dynactin 复合物在体内的正确组装。

VezA/vezatin facilitates proper assembly of the dynactin complex in vivo.

机构信息

Department of Biochemistry and Molecular Biology, The Uniformed Services University of the Health Sciences - F. Edward Hébert School of Medicine, Bethesda, MD 20814, USA.

Department of Biochemistry and Molecular Biology, The Uniformed Services University of the Health Sciences - F. Edward Hébert School of Medicine, Bethesda, MD 20814, USA; Montgomery Blair High School, Silver Spring, MD, USA.

出版信息

Cell Rep. 2024 Nov 26;43(11):114943. doi: 10.1016/j.celrep.2024.114943. Epub 2024 Nov 1.

Abstract

Cytoplasmic dynein-mediated intracellular transport needs the multi-component dynactin complex for cargo binding and motor activation. However, the cellular factors involved in dynactin assembly remain unexplored. Here, we found in Aspergillus nidulans that the vezatin homolog VezA is important for dynactin assembly. VezA affects the microtubule plus-end accumulation of dynein before cargo binding and cargo-adapter-mediated dynein activation, two processes that both need dynactin. The dynactin complex contains multiple components, including p150, p50, and an Arp1 (actin-related protein 1) mini-filament associated with a pointed-end sub-complex. VezA physically interacts with the Arp1 mini-filament either directly or indirectly. Loss of VezA significantly decreases the amount of Arp1 pulled down with pointed-end proteins, as well as the protein levels of p50 and p150 in cell extract. Using various dynactin mutants, we further revealed that the dynactin assembly process must be highly coordinated. Together, these results shed light on dynactin assembly in vivo.

摘要

细胞质动力蛋白介导的细胞内运输需要多组分动力蛋白激活因子复合物来结合货物和激活马达。然而,参与动力蛋白激活因子组装的细胞因子仍未被探索。在这里,我们在构巢曲霉中发现了 vezatin 同源物 VezA 对于动力蛋白激活因子复合物组装是重要的。在货物结合和货物适配器介导的动力蛋白激活之前,VezA 影响微管正极端动力蛋白的积累,这两个过程都需要动力蛋白激活因子复合物。动力蛋白激活因子复合物包含多个成分,包括 p150、p50 和与尖头端亚复合物相关的 Arp1(肌动蛋白相关蛋白 1)微丝。VezA 直接或间接与 Arp1 微丝相互作用。VezA 的缺失显著降低了与尖头端蛋白一起下拉的 Arp1 的量,以及细胞提取物中 p50 和 p150 的蛋白水平。使用各种动力蛋白激活因子突变体,我们进一步揭示了动力蛋白激活因子复合物组装过程必须高度协调。总之,这些结果阐明了体内的动力蛋白激活因子复合物组装过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f5/11661459/279a8d43e3a4/nihms-2038912-f0002.jpg

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