Unique regulatory properties of the type 2a Ca2+ channel β subunit caused by palmitoylation
Unique regulatory properties of the type 2a Ca2+ channel β subunit caused by palmitoylation
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DOI：
10.1073/pnas.95.8.4690
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发表时间：
1998-04-14
影响因子：
11.1
通讯作者：
Birnbaumer, L
中科院分区：
文献类型：
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作者：
Qin, N;Platano, D;Birnbaumer, L
电压门控Ca 2+通道的β亚基由四种基因编码，并由于选择性剪接而显示出额外的分子多样性。在功能水平上，除β 2a外，所有形式都非常相似，不同之处在于它不支持α（1C）Ca 2+通道的前脉冲易化，抑制神经元α（1 E）Ca 2+通道的电压诱导失活，并且更有效地阻断G蛋白偶联受体对α（1 E）通道的抑制。我们表明，β 2a的区别性，而不是与α（1）的一个独特的网站的相互作用，是因为最近描述的棕榈酰化的半胱氨酸在位置3和4，这也发生在非洲爪蟾卵母细胞。基本上，β 2a的所有区别特征在不能被棕榈酰化的突变体中丢失[β 2a（Cys（3，4）Ser）]。由于蛋白质棕榈酰化是一个动态的过程，这些研究结果指出，棕榈酰化的调节可能有助于活动依赖性神经元和突触可塑性的可能性。有证据表明，可能存在多达三个β 2剪接变体不同，只有在其N-末端。
beta subunits of voltage-gated Ca2+ channels are encoded in four genes and display additional molecular diversity because of alternative splicing. At the functional level, all forms are very-similar except for beta 2a, which differs in that it does not support prepulse facilitation of alpha(1C) Ca2+ channels, inhibits voltage-induced inactivation of neuronal alpha(1E) Ca2+ channels, and is more effective in blocking inhibition of alpha(1E) channels by G protein-coupled receptors. We show that the distinguishing properties of beta 2a, rather than interaction with a distinct site of alpha(1), are because of the recently described palmitoylation of cysteines in positions three and four, which also occurs in the Xenopus oocyte. Essentially, all of the distinguishing features of beta 2a were lost in a mutant that could not be palmitoylated [beta 2a(Cys(3,4)Ser)]. Because protein palmitoylation is a dynamic process, these findings point to the possibility that regulation of palmitoylation may contribute to activity-dependent neuronal and synaptic plasticity. Evidence is presented that there may exist as many as three beta 2 splice variants differing only in their N-termini.