Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
Synapse. 2013 Aug;67(8):532-40. doi: 10.1002/syn.21657. Epub 2013 Mar 20.
Best known for its interaction with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluA2 and for its influence on excitatory synapse activity, the protein interacting with C kinase, PICK1, is the focus of considerable attention from neurobiologists. Indeed, this PSD-95/DlgA/ZO-1 (PDZ) domain-containing protein has been shown to interact with a wide variety of neurotransmitter receptors, transporters, and enzymes, including glutamate and nicotinic acetylcholine receptors, dopamine and glutamate transporters, and the enzyme serine racemase. Through its lipid binding domain, PICK1 is targeted to the inner surface of the cell membrane where it contributes to anchoring these partners and thereby influences their synaptic localization and function. Under pathological conditions, the regulation of some PICK1-interacting partners is altered, pointing to an involvement of PICK1 in neurological disorders. Also, genetic or pharmacological manipulations of PICK1 expression, localization, or function have been shown to influence several physiological or pathological processes in which putative PICK1 partners are involved. This review will summarize recent experimental observations that highlight the involvement of PICK1 in neurological disorders, including schizophrenia, Parkinson's disease, epilepsy, chronic pain, drug abuse, and amyotrophic lateral sclerosis.
作为与α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚基 GluA2 相互作用和影响兴奋性突触活动而闻名的蛋白质，蛋白相互作用激酶 1（PICK1）是神经生物学家关注的焦点。事实上，这种富含 PDZ 结构域的蛋白已被证明与多种神经递质受体、转运体和酶相互作用，包括谷氨酸和烟碱型乙酰胆碱受体、多巴胺和谷氨酸转运体，以及酶丝氨酸 racemase。通过其脂质结合结构域，PICK1 被靶向到细胞膜的内表面，在那里它有助于锚定这些伴侣，从而影响它们的突触定位和功能。在病理条件下，一些 PICK1 相互作用伙伴的调节发生改变，表明 PICK1 参与了神经疾病。此外，PICK1 表达、定位或功能的遗传或药理学操作已被证明会影响一些涉及假定 PICK1 伙伴的生理或病理过程。这篇综述将总结最近的实验观察结果，强调 PICK1 在神经疾病中的作用，包括精神分裂症、帕金森病、癫痫、慢性疼痛、药物滥用和肌萎缩侧索硬化症。
