Browning Heidi, Hackney David D, Nurse Paul
Cell Cycle Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK.
Nat Cell Biol. 2003 Sep;5(9):812-8. doi: 10.1038/ncb1034. Epub 2003 Aug 3.
Kinesins are microtubule-based motor proteins that transport cargo to specific locations within the cell. However, the mechanisms by which cargoes are directed to specific cellular locations have remained elusive. Here, we investigated the in vivo movement of the Schizosaccharomyces pombe kinesin Tea2 to establish how it is targeted to microtubule tips and cell ends. Tea2 is loaded onto microtubules in the middle of the cell, in close proximity to the nucleus, and then travels using its intrinsic motor activity primarily at the tips of polymerizing microtubules. The microtubule-associated protein Mal3, an EB1 homologue, is required for loading and/or processivity of Tea2 and this function can be substituted by human EB1. In addition, the cell-end marker Tea1 is required to anchor Tea2 to cell ends. Movement of Tea1 and the CLIP170 homologue Tip1 to cell ends is abolished in Tea2 rigor (ATPase) mutants. We propose that microtubule-based transport from the vicinity of the nucleus to cell ends can be precisely regulated, with Mal3 required for loading/processivity, Tea2 for movement and Tea1 for cell-end anchoring.
驱动蛋白是基于微管的马达蛋白，可将货物运输到细胞内的特定位置。然而，货物被导向特定细胞位置的机制仍然难以捉摸。在这里，我们研究了粟酒裂殖酵母驱动蛋白Tea2在体内的运动，以确定它是如何被靶向到微管末端和细胞末端的。Tea2在细胞中部靠近细胞核的位置加载到微管上，然后主要利用其内在的马达活性在聚合微管的末端移动。微管相关蛋白Mal3是一种EB1同源物，是Tea2加载和/或持续运动所必需的，并且该功能可以被人类EB1替代。此外，细胞末端标记物Tea1是将Tea2锚定到细胞末端所必需的。在Tea2严格（ATP酶）突变体中，Tea1和CLIP170同源物Tip1向细胞末端的移动被消除。我们提出，从细胞核附近到细胞末端的基于微管的运输可以被精确调控，Mal3用于加载/持续运动，Tea2用于移动，Tea1用于细胞末端锚定。
