How does alternate splicing of a sodium channel gene generate diversity in neuronal signalling?

人类大脑包含数量惊人的神经细胞（神经元），它们相互之间形成连接网络（突触）。这些神经回路控制着我们所做的几乎所有事情，包括呼吸、行走和学习等行为。行为的多样性反映在个体神经细胞功能相似程度的多样性需求上。因此，神经元在它们接触的目标、它们释放的信号化学物质（神经递质）以及它们能够激发触发其神经递质释放的电动作电位的方式方面有所不同。事实上，这些特征的多样性程度可能比基因组中存在的基因数量大几个数量级，因此需要额外的机制。最近的研究表明，额外的多样性至少部分是由于相同基因产生的不同蛋白质产物。所谓的选择性剪接，导致多个相关蛋白质在一个基因内编码。产生的每种蛋白质变体都具有赋予表达发生的神经元不同特性的能力。虽然现在已经建立，但剪接如何引起神经元功能的变化仍有待研究。我们使用果蝇是因为它非常适合遗传分析，完整的基因组已经测序，因为它提供了一个简单的人类神经系统模型。我们的研究将告诉我们，我们自己的神经细胞如何能够发展成具有彼此不同的特性。

The human brain contains a staggeringly large number of nerve cells (neurons) that form networks of connections (synapses) with one another. These neuronal circuits control almost everything we do, including behaviours such as breathing, walking and learning. Diversity of behaviour is mirrored by the need for a similar degree of diversity of function of individual nerve cells. Thus, neurons differ in the target that they contact, the signalling chemicals (neurotransmitters) they release, and the way in which they are able to fire electrical action potentials that trigger release of their neurotransmitter(s). Indeed, the degree of diversity of these characteristics is likely orders of magnitude greater than the number of genes present in the genome and, as such, additional mechanisms are required. Recent research suggests that additional diversity is due, at least in part, to different protein products being produced from the same genes. Alternate splicing, as this is called, results in multiple related proteins being encoded within one gene. Each protein variant produced has the capability of conferring different properties to the neuron in which expression occurs. Although now established, it remains largely to be shown how splicing induces changes to neuron function. We use the fruitfly because it is very amenable to genetic analysis, the complete genome has been sequenced, and because it provides a simple model of the human nervous system. Our study will inform us how our own nerve cells are able to develop to have different properties from one another.