Xu Junyu, Wang Na, Luo Jian-Hong, Xia Jun
Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, P.R. China.
Division of Life Science, Division of Biomedical Engineering, and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Sci Rep. 2016 Feb 12;6:20924. doi: 10.1038/srep20924.
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.
PICK1（与C激酶1相互作用的蛋白质）是一种外周膜蛋白，可与多种膜蛋白相互作用。研究表明，PICK1可调节突触受体的聚集和膜定位，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ASICs（酸敏感离子通道）。此外，最近的证据表明，在包括神经元在内的多种细胞系统中，PICK1可介导各种囊泡从高尔基体复合体输出。然而，PICK1如何影响囊泡运输动力学仍未得到探索。在这里，我们表明PICK1通过与syntabulin相互作用来介导囊泡运输，syntabulin是一种驱动蛋白结合蛋白，可介导轴突中突触囊泡和线粒体的运输。Syntabulin将PICK1募集到微管结构上，并介导含PICK1的囊泡沿微管运输。在神经元中，syntabulin通过将PICK1募集到轴突中来改变PICK1的表达，并调节含PICK1的囊泡的运输动力学。此外，我们表明syntabulin与PICK1和ASICs形成复合物，调节神经元中ASIC蛋白的表达，并参与ASIC诱导的酸毒性。
