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原肌球蛋白 1-I/C 在 Oskar mRNA 运输过程中协调驱动蛋白-1 和动力蛋白。

Tropomyosin 1-I/C coordinates kinesin-1 and dynein motors during oskar mRNA transport.

机构信息

Developmental Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.

Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, UK.

出版信息

Nat Struct Mol Biol. 2024 Mar;31(3):476-488. doi: 10.1038/s41594-024-01212-x. Epub 2024 Jan 31.

DOI:10.1038/s41594-024-01212-x
PMID:38297086
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10948360/
Abstract

Dynein and kinesin motors mediate long-range intracellular transport, translocating towards microtubule minus and plus ends, respectively. Cargoes often undergo bidirectional transport by binding to both motors simultaneously. However, it is not known how motor activities are coordinated in such circumstances. In the Drosophila female germline, sequential activities of the dynein-dynactin-BicD-Egalitarian (DDBE) complex and of kinesin-1 deliver oskar messenger RNA from nurse cells to the oocyte, and within the oocyte to the posterior pole. We show through in vitro reconstitution that Tm1-I/C, a tropomyosin-1 isoform, links kinesin-1 in a strongly inhibited state to DDBE-associated oskar mRNA. Nuclear magnetic resonance spectroscopy, small-angle X-ray scattering and structural modeling indicate that Tm1-I/C suppresses kinesin-1 activity by stabilizing its autoinhibited conformation, thus preventing competition with dynein until kinesin-1 is activated in the oocyte. Our work reveals a new strategy for ensuring sequential activity of microtubule motors.

摘要

动力蛋白和肌球蛋白马达介导长距离细胞内运输，分别向微管的负端和正端移动。货物通常通过同时与两个马达结合而进行双向运输。然而，在这种情况下，马达活动是如何协调的还不得而知。在果蝇雌性生殖细胞中，动力蛋白-dynactin-BicD-Egalitarian (DDBE) 复合物和肌球蛋白-1 的顺序活性将 Oskar 信使 RNA 从滋养细胞运送到卵母细胞，并在卵母细胞内运送到后极。我们通过体外重建表明，一种肌球蛋白-1 结合蛋白 Tm1-I/C 将肌球蛋白-1 与 DDBE 相关的 Oskar mRNA 以强烈抑制状态连接起来。核磁共振波谱、小角度 X 射线散射和结构建模表明，Tm1-I/C 通过稳定其自身抑制构象来抑制肌球蛋白-1 的活性，从而防止其与动力蛋白竞争，直到肌球蛋白-1在卵母细胞中被激活。我们的工作揭示了一种确保微管马达顺序活性的新策略。

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