Syntabulin regulates the trafficking of PICK1-containing vesicles in neurons.
Syntabulin regulates the trafficking of PICK1-containing vesicles in neurons.
复制标题
Syntabulin 调节神经元中含有 PICK1 的囊泡的运输。
DOI：
10.1038/srep20924
复制
发表时间：
2016-02-12
影响因子：
4.6
通讯作者：
Xia J
中科院分区：
文献类型：
--
作者：
Xu J;Wang N;Luo JH;Xia J
PICK 1（与C-激酶1相互作用的蛋白质）是一种与多种膜蛋白相互作用的外周膜蛋白。PICK 1已被证明可调节突触受体如AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）受体、代谢型谷氨酸受体7和ASIC（酸敏感离子通道）的聚集和膜定位。此外，最近的证据表明，PICK 1可以介导多种囊泡从包括神经元在内的几种细胞系统中的高尔基复合体中运输出来。然而，PICK 1如何影响囊泡运输动力学仍然未被探索。在这里，我们表明，PICK 1介导的囊泡贩运与syntabulin，驱动蛋白结合蛋白，介导的突触囊泡和轴突中的线粒体的贩运相互作用。Syntabulin将PICK 1募集到微管结构上，并介导含PICK 1的囊泡沿着微管的运输。在神经元中，syntabulin通过将PICK 1募集到轴突中来改变PICK 1的表达，并调节含有PICK 1的囊泡的运输动力学。此外，我们表明，syntabulin形成一个复杂的PICK 1和ASIC，调节ASIC蛋白在神经元中的表达，并参与ASIC诱导的酸毒性。
PICK1 (protein interacting with C-kinase 1) is a peripheral membrane protein that interacts with diverse membrane proteins. PICK1 has been shown to regulate the clustering and membrane localization of synaptic receptors such as AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, metabotropic glutamate receptor 7, and ASICs (acid-sensing ion channels). Moreover, recent evidence suggests that PICK1 can mediate the trafficking of various vesicles out from the Golgi complex in several cell systems, including neurons. However, how PICK1 affects vesicle-trafficking dynamics remains unexplored. Here, we show that PICK1 mediates vesicle trafficking by interacting with syntabulin, a kinesin-binding protein that mediates the trafficking of both synaptic vesicles and mitochondria in axons. Syntabulin recruits PICK1 onto microtubule structures and mediates the trafficking of PICK1-containing vesicles along microtubules. In neurons, syntabulin alters PICK1 expression by recruiting PICK1 into axons and regulates the trafficking dynamics of PICK1-containing vesicles. Furthermore, we show that syntabulin forms a complex with PICK1 and ASICs, regulates ASIC protein expression in neurons, and participates in ASIC-induced acidotoxicity.