Department of Biomedical Engineering, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Nat Rev Mol Cell Biol. 2014 Sep;15(9):615-28. doi: 10.1038/nrm3853. Epub 2014 Aug 16.
Vesicles, organelles and other intracellular cargo are transported by kinesin and dynein motors, which move in opposite directions along microtubules. This bidirectional cargo movement is frequently described as a 'tug of war' between oppositely directed molecular motors attached to the same cargo. However, although many experimental and modelling studies support the tug-of-war paradigm, numerous knockout and inhibition studies in various systems have found that inhibiting one motor leads to diminished motility in both directions, which is a 'paradox of co-dependence' that challenges the paradigm. In an effort to resolve this paradox, three classes of bidirectional transport models--microtubule tethering, mechanical activation and steric disinhibition--are proposed, and a general mathematical modelling framework for bidirectional cargo transport is put forward to guide future experiments.
囊泡、细胞器和其他细胞内货物由驱动蛋白和动力蛋白马达运输,这些马达沿着微管向相反的方向移动。这种双向货物运动通常被描述为附着在同一货物上的相反方向分子马达之间的“拔河比赛”。然而,尽管许多实验和建模研究支持拔河比赛范式,但在各种系统中的许多敲除和抑制研究发现,抑制一个马达会导致两个方向的运动能力下降,这是一个“相互依赖的悖论”,挑战了这一范式。为了解决这一悖论,提出了三类双向运输模型——微管连接、机械激活和空间抑制解除,并提出了一个用于指导未来实验的双向货物运输的通用数学建模框架。
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