ASIC subunit ratio and differential surface trafficking in the brain.
ASIC subunit ratio and differential surface trafficking in the brain.
复制标题
ASIC亚基比和大脑中的差异表面运输。
DOI：
10.1186/s13041-016-0185-7
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发表时间：
2016-01-08
期刊：
影响因子：
3.6
通讯作者：
Zha XM
中科院分区：
文献类型：
--
作者：
Wu J;Xu Y;Jiang YQ;Xu J;Hu Y;Zha XM
酸敏感离子通道（ASIC）是神经元酸中毒反应的关键介质。然而，人们对大脑中不同ASIC亚基的相对丰度知之甚少。这些数据对于解释ASIC 1a同聚体和1a/2异聚体对酸信号传导的相对贡献是至关重要的，并且对于设计针对这些通道的治疗干预措施至关重要。我们采用一种简单的生化方法，半定量测定了小鼠脑中ASIC 1a和2亚基的摩尔比。此外，我们研究了ASIC 1a、ASIC 2a和ASIC 2b的差异表面运输。ASIC 1a亚基的数量超过ASIC 2a和ASIC 2b的总和。ASIC 2a和2b表达存在区域特异性变化，小脑和纹状体分别主要表达2b和2a。此外，我们进行了表面生物素化，发现表面ASIC 1a和ASIC 2a的比例与它们的总表达相关。相比之下，ASIC 2b在大脑中表现出很少的表面存在。该结果与ASIC 2b与ER标志物在3 T3细胞中的共定位增加一致。我们的数据是第一个半定量测定脑中各种ASIC的相对亚基比例。ASICs的差异表面运输表明，大脑中的主要功能ASICs是ASIC 1a同源体和1a/2a异源体。这一发现为各种ASIC复合物对神经元中酸信号传导的相对贡献提供了重要的见解。
Acid-sensing ion channels (ASICs) are key mediators of acidosis-induced responses in neurons. However, little is known about the relative abundance of different ASIC subunits in the brain. Such data are fundamental for interpreting the relative contribution of ASIC1a homomers and 1a/2 heteromers to acid signaling, and essential for designing therapeutic interventions to target these channels. We used a simple biochemical approach and semi-quantitatively determined the molar ratio of ASIC1a and 2 subunits in mouse brain. Further, we investigated differential surface trafficking of ASIC1a, ASIC2a, and ASIC2b. ASIC1a subunits outnumber the sum of ASIC2a and ASIC2b. There is a region-specific variation in ASIC2a and 2b expression, with cerebellum and striatum expressing predominantly 2b and 2a, respectively. Further, we performed surface biotinylation and found that surface ASIC1a and ASIC2a ratio correlates with their total expression. In contrast, ASIC2b exhibits little surface presence in the brain. This result is consistent with increased co-localization of ASIC2b with an ER marker in 3T3 cells. Our data are the first semi-quantitative determination of relative subunit ratio of various ASICs in the brain. The differential surface trafficking of ASICs suggests that the main functional ASICs in the brain are ASIC1a homomers and 1a/2a heteromers. This finding provides important insights into the relative contribution of various ASIC complexes to acid signaling in neurons.