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一条轴突,众多驱动蛋白:其中的逻辑是什么?

One axon, many kinesins: What's the logic?

作者信息

Muresan V

机构信息

Department of Cell Biology, Harvard Medical School, Boston, MA, USA.

出版信息

J Neurocytol. 2000 Nov-Dec;29(11-12):799-818. doi: 10.1023/a:1010943424272.

Abstract

A large number of membrane-bounded organelles, protein complexes, and mRNAs are transported along microtubules to different locations within the neuronal axon. Axonal transport in the anterograde direction is carried out by members of a superfamily of specialized motor proteins, the kinesins. All kinesins contain a conserved motor domain that hydrolyses ATP to generate movement along microtubules. Regions outside the motor domain are responsible for cargo binding and regulation of motor activity. Present in a soluble, inactive form in the cytoplasm, kinesins are activated upon cargo binding. Selective targeting of different types of kinesin motors to specific cargoes is directed by amino acid sequences situated in their variable tails. Cargo proteins with specific function at their destination, bind directly to specific kinesins for transport. Whereas most kinesins move to microtubule plus-ends, a small number of them move to microtubule minus-ends, and may participate in retrograde axonal transport. Axonal transport by kinesins has a logic: Fully assembled, multisubunit, functional complexes (e.g., ion channel complexes, signaling complexes, RNA-protein complexes) are transported to their destination by kinesin motors that interact transiently (i.e., during transport only) with one of the complexes' subunits.

摘要

大量的膜结合细胞器、蛋白质复合物和信使核糖核酸沿着微管被运输到神经元轴突内的不同位置。顺行方向的轴突运输由一类特殊的运动蛋白——驱动蛋白超家族的成员来完成。所有的驱动蛋白都含有一个保守的运动结构域,该结构域水解三磷酸腺苷以产生沿微管的运动。运动结构域之外的区域负责货物结合和运动活性的调节。驱动蛋白以可溶性的无活性形式存在于细胞质中,在与货物结合后被激活。不同类型的驱动蛋白马达对特定货物的选择性靶向是由位于其可变尾部的氨基酸序列指导的。在目的地具有特定功能的货物蛋白直接与特定的驱动蛋白结合以进行运输。虽然大多数驱动蛋白向微管的正端移动,但其中少数向微管的负端移动,并可能参与逆行轴突运输。驱动蛋白介导的轴突运输有一个逻辑:完全组装好的、多亚基的功能复合物(如离子通道复合物、信号复合物、核糖核蛋白复合物)由驱动蛋白马达运输到其目的地,这些马达与复合物的一个亚基短暂相互作用(即仅在运输过程中)。

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