Hruska-Hageman Alesia M, Benson Christopher J, Leonard A Soren, Price Margaret P, Welsh Michael J
Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
J Biol Chem. 2004 Nov 5;279(45):46962-8. doi: 10.1074/jbc.M405874200. Epub 2004 Aug 17.
The acid-sensing ion channel-3 (ASIC3) is a degenerin/epithelial sodium channel expressed in the peripheral nervous system. Previous studies indicate that it participates in the response to mechanical and painful stimuli, perhaps contributing to mechanoreceptor and/or H+ -gated nociceptor function. ASIC3 subunits contain intracellular N and C termini that may control channel localization and function. We found that a PDZ-binding motif at the ASIC3 C terminus interacts with four different proteins that contain PDZ domains: PSD-95, Lin-7b, MAGI-1b, and PIST. ASIC3 and these interacting proteins were expressed in dorsal root ganglia and spinal cord, and PSD-95 co-precipitated ASIC3 from spinal cord. When expressed in heterologous cells, PSD-95 reduced the amplitude of ASIC3 acid-evoked currents, whereas Lin-7b increased current amplitude. PSD-95 and Lin-7b altered current density by decreasing or increasing, respectively, the amount of ASIC3 on the cell surface. The finding that multiple PDZ-containing proteins bind ASIC3 and can influence its presence in the plasma membrane suggests that they may play an important role in the contribution of ASIC3 to nociception and mechanosensation.
酸敏感离子通道3（ASIC3）是一种在周围神经系统中表达的退化蛋白/上皮钠通道。先前的研究表明，它参与对机械和疼痛刺激的反应，可能有助于机械感受器和/或H⁺门控伤害感受器的功能。ASIC3亚基包含细胞内的N端和C端，它们可能控制通道的定位和功能。我们发现，ASIC3 C端的一个PDZ结合基序与四种含有PDZ结构域的不同蛋白质相互作用：PSD-95、Lin-7b、MAGI-1b和PIST。ASIC3和这些相互作用的蛋白质在背根神经节和脊髓中表达，并且PSD-95从脊髓中共沉淀出ASIC3。当在异源细胞中表达时，PSD-95降低了ASIC3酸诱发电流的幅度，而Lin-7b增加了电流幅度。PSD-95和Lin-7b分别通过减少或增加细胞表面ASIC3的量来改变电流密度。多种含PDZ的蛋白质与ASIC3结合并能影响其在质膜中的存在这一发现表明，它们可能在ASIC3对伤害感受和机械感觉的贡献中起重要作用。
