Nde1 and Ndel1: Outstanding Mysteries in Dynein-Mediated Transport.

Nde1 and Ndel1: Outstanding Mysteries in Dynein-Mediated Transport.
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DOI:
10.3389/fcell.2022.871935
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发表时间:
2022
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
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--
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细胞质动力蛋白-1(动力蛋白)是大多数真核生物中主要的微管负端定向分子马达。因此,动力蛋白具有广泛的功能,从驱动逆行定向货物运输到形成和聚焦有丝分裂纺锤体。动力蛋白不能单独发挥作用。相反,调节蛋白网络介导动力蛋白与货物的相互作用,并调节动力蛋白与微管轨道结合和移动的能力。过去十年的一系列研究揭示了许多动力蛋白调节因子的功能和机制,包括 Lis1、dynactin 和称为激活适配器的蛋白质家族。然而,动力蛋白的两个重要结合伙伴(旁系同源物 Nde1 和 Ndel1)的机制细节仍然难以捉摸。虽然遗传学研究已确定 Nde1/Ndel1 作为动力蛋白运输途径的参与者,但它们如何调节动力蛋白活性的性质尚不清楚。在这篇综述中,我们将比较 Ndel1 和 Nde1,重点是辨别蛋白质是否在功能上冗余,概述将 Nde1/Ndel1 置于动力蛋白运输途径中的数据,并探索支持和反对 Nde1/Ndel1 对动力蛋白活性的分子影响的主要假设的文献。
Cytoplasmic dynein-1 (dynein) is the primary microtubule minus-end directed molecular motor in most eukaryotes. As such, dynein has a broad array of functions that range from driving retrograde-directed cargo trafficking to forming and focusing the mitotic spindle. Dynein does not function in isolation. Instead, a network of regulatory proteins mediate dynein’s interaction with cargo and modulate dynein’s ability to engage with and move on the microtubule track. A flurry of research over the past decade has revealed the function and mechanism of many of dynein’s regulators, including Lis1, dynactin, and a family of proteins called activating adaptors. However, the mechanistic details of two of dynein’s important binding partners, the paralogs Nde1 and Ndel1, have remained elusive. While genetic studies have firmly established Nde1/Ndel1 as players in the dynein transport pathway, the nature of how they regulate dynein activity is unknown. In this review, we will compare Ndel1 and Nde1 with a focus on discerning if the proteins are functionally redundant, outline the data that places Nde1/Ndel1 in the dynein transport pathway, and explore the literature supporting and opposing the predominant hypothesis about Nde1/Ndel1’s molecular effect on dynein activity.
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