Institute of Structural and Molecular Biology, Birkbeck College, London, WC1E 7HX, UK.
Biol Cell. 2013 Oct;105(10):465-87. doi: 10.1111/boc.201300012. Epub 2013 Jul 25.
In the crowded environment of eukaryotic cells, diffusion is an inefficient distribution mechanism for cellular components. Long-distance active transport is required and is performed by molecular motors including kinesins. Furthermore, in highly polarised, compartmentalised and plastic cells such as neurons, regulatory mechanisms are required to ensure appropriate spatio-temporal delivery of neuronal components. The kinesin machinery has diversified into a large number of kinesin motor proteins as well as adaptor proteins that are associated with subsets of cargo. However, many mechanisms contribute to the correct delivery of these cargos to their target domains. One mechanism is through motor recognition of sub-domain-specific microtubule (MT) tracks, sign-posted by different tubulin isoforms, tubulin post-translational modifications, tubulin GTPase activity and MT-associated proteins (MAPs). With neurons as a model system, a critical review of these regulatory mechanisms is presented here, with a particular focus on the emerging contribution of compartmentalised MAPs. Overall, we conclude that - especially for axonal cargo - alterations to the MT track can influence transport, although in vivo, it is likely that multiple track-based effects act synergistically to ensure accurate cargo distribution.
在真核细胞拥挤的环境中，扩散是细胞成分的一种低效分配机制。需要进行长距离的主动运输，而这是由包括驱动蛋白在内的分子马达来完成的。此外，在高度极化、区室化和可塑性的细胞（如神经元）中，需要调节机制来确保神经元成分的适当时空传递。驱动蛋白机制已经多样化为大量的驱动蛋白马达蛋白以及与货物亚群相关的衔接蛋白。然而，许多机制有助于这些货物正确地递送到它们的目标区域。一种机制是通过马达蛋白识别由不同微管（MT）亚型、微管蛋白翻译后修饰、MT GTP 酶活性和 MT 相关蛋白（MAP）标记的亚域特异性 MT 轨道。本文以神经元作为模型系统，对这些调节机制进行了批判性的回顾，特别关注区室化 MAP 的新出现的贡献。总的来说，我们的结论是 - 特别是对于轴突货物 - MT 轨道的改变会影响运输，尽管在体内，可能有多种基于轨道的效应协同作用以确保准确的货物分布。
