The role of palmitoylation in functional expression of nicotinic α7 receptors
The role of palmitoylation in functional expression of nicotinic α7 receptors
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DOI：
10.1523/jneurosci.3315-04.2004
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发表时间：
2004-11-17
影响因子：
5.3
通讯作者：
Green, WN
中科院分区：
文献类型：
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作者：
Drisdel, RC;Manzana, E;Green, WN
神经元α-银环蛇毒素受体（BgtR）是烟碱受体，其需要尚未鉴定的翻译后修饰以实现功能性表达。在这项研究中，我们研究了蛋白棕榈酰化在BgtR表达中的作用。BgtR α 7亚基在来自脑的神经元和能够表达BgtR的其它细胞（例如嗜铬细胞瘤12（PC 12）细胞）中高度棕榈酰化。在PC 12细胞中，alpha 7亚基被棕榈酰化，每个亚基大约有一个棕榈酸酯，抑制棕榈酰化会阻断BgtR的表达。在不能表达BgtR的细胞中，如人胚肾细胞，α 7亚基没有被显著棕榈酰化。然而，在这些相同的细胞中，α 7的N-末端一半与5-羟色胺-3A受体（α 7/5-HT 3A）亚基的C-末端一半融合的嵌合亚基形成功能性BgtR，其棕榈酰化程度与PC 12细胞中的BgtR α 7亚基相似。PC 12和α 7/5-HT 3A BgtR的棕榈酰化发生在内质网（ER）中组装期间。总之，我们的数据表明蛋白质棕榈酰化的功能，其中ER中组装α 7亚基的棕榈酰化在功能性BgtR的形成中起作用。
Neuronal alpha-bungarotoxin receptors (BgtRs) are nicotinic receptors that require as yet unidentified post-translational modifications to achieve functional expression. In this study, we examined the role of protein palmitoylation in BgtR expression. BgtR alpha7 subunits are highly palmitoylated in neurons from brain and other cells capable of BgtR expression, such as pheochromocytoma 12 (PC12) cells. In PC12 cells, alpha7 subunits are palmitoylated with a stoichiometry of approximately one palmitate per subunit, and inhibition of palmitoylation blocks BgtR expression. In cells incapable of BgtR expression, such as human embryonic kidney cells, alpha7 subunits are not significantly palmitoylated. However, in these same cells, chimeric subunits with the N-terminal half of alpha7 fused to the C-terminal half of serotonin-3A receptor (alpha7/5-HT3A) subunits form functional BgtRs that are palmitoylated to an extent similar to that of BgtR alpha7 subunits in PC12 cells. Palmitoylation of PC12 and alpha7/5-HT3A BgtRs occurred during assembly in the endoplasmic reticulum ( ER). In conclusion, our data indicate a function for protein palmitoylation in which palmitoylation of assembling alpha7 subunits in the ER has a role in the formation of functional BgtRs.