Kumari Amrita, Kumar Chandan, Wasnik Neeraj, Mylavarapu Sivaram V S
Laboratory of Cellular Dynamics, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad, Haryana 121001, India.
Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
J Cell Sci. 2021 May 15;134(10). doi: 10.1242/jcs.254870. Epub 2021 May 20.
In animal cells, a single cytoplasmic dynein motor mediates microtubule minus-end-directed transport, counterbalancing dozens of plus-end-directed kinesins. The remarkable ability of dynein to interact with a diverse cargo spectrum stems from its tightly regulated recruitment of cargo-specific adaptor proteins, which engage the dynactin complex to make a tripartite processive motor. Adaptor binding is governed by the homologous dynein light intermediate chain subunits LIC1 (DYNC1LI1) and LIC2 (DYNC1LI2), which exist in mutually exclusive dynein complexes that can perform both unique and overlapping functions. The intrinsically disordered and variable C-terminal domains of the LICs are indispensable for engaging a variety of structurally divergent adaptors. Here, we hypothesize that numerous spatiotemporally regulated permutations of posttranslational modifications of the LICs, as well as of the adaptors and cargoes, exponentially expand the spectrum of dynein-adaptor-cargo complexes. We thematically illustrate the possibilities that could generate a vast set of biochemical variations required to support the wide range of dynein functions.
在动物细胞中，单个胞质动力蛋白介导微管负端定向运输，平衡数十种正端定向的驱动蛋白。动力蛋白与多种货物相互作用的卓越能力源于其对货物特异性衔接蛋白的严格招募，这些衔接蛋白与动力蛋白激活蛋白复合物结合，形成一个三方连续性马达。衔接蛋白的结合由同源的动力蛋白轻中间链亚基LIC1（DYNC1LI1）和LIC2（DYNC1LI2）控制，它们存在于相互排斥的动力蛋白复合物中，这些复合物可以执行独特和重叠的功能。LICs内在无序且可变的C末端结构域对于结合各种结构不同的衔接蛋白是不可或缺的。在这里，我们假设LICs以及衔接蛋白和货物的翻译后修饰在时空上受到多种调控，这将以指数方式扩展动力蛋白-衔接蛋白-货物复合物的范围。我们从主题上说明了可能产生大量生化变异的可能性，这些变异是支持动力蛋白广泛功能所必需的。
