Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2.
Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2.
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DOI：
10.1038/srep27456
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发表时间：
2016-06-07
影响因子：
4.6
通讯作者：
Allan VJ
中科院分区：
文献类型：
--
作者：
Ruane PT;Gumy LF;Bola B;Anderson B;Wozniak MJ;Hoogenraad CC;Allan VJ
微管及其相关蛋白（MAPs）支撑着特化细胞的极性。大肠腺瘤性息肉病（APC）就是这样一种具有多功能议程的MAP，需要精确的细胞内定位。尽管APC已被发现与激酶2亚家族成员相关，但APC外周定位的确切机制尚不清楚。在这里，我们发现激酶-1的重链直接与APC c端相互作用，有助于APC在成纤维细胞中的外周定位。在大鼠海马神经元中，APC的驱动蛋白-1结合域是其轴突尖端富集所必需的。此外，我们证明APC需要与激酶-2和激酶-1相互作用才能实现这种定位。缺乏激酶1结合域的APC表达的神经元轴突较短，强调了激酶1关联的重要性。这种新的激酶-1-APC相互作用的鉴定突出了APC在神经元中定位的复杂性和重要性。
Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members, the exact mechanism for the peripheral localization of APC remains unclear. Here we show that the heavy chain of kinesin-1 directly interacts with the APC C-terminus, contributing to the peripheral localisation of APC in fibroblasts. In rat hippocampal neurons the kinesin-1 binding domain of APC is required for its axon tip enrichment. Moreover, we demonstrate that APC requires interactions with both kinesin-2 and kinesin-1 for this localisation. Underlining the importance of the kinesin-1 association, neurons expressing APC lacking kinesin-1-binding domain have shorter axons. The identification of this novel kinesin-1-APC interaction highlights the complexity and significance of APC localisation in neurons.