ADDUCIN REGULATES THE NEUROMUSCULAR JUNCTION IN DROSOPHILA

内收蛋白调节果蝇的神经肌肉接头

• 批准号: 171372-2012
• 负责人: Krieger, Charles
• 金额: $ 1.89万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=593597
• 关键词: ADDUCIN; REGULATES; NEUROMUSCULAR; JUNCTION; DROSOPHILA

Nerve cells communicate with one another at junctions termed synapses; when a neuron connects to muscle, the connecting synapse is called a neuromuscular junction (NMJ). The NMJ is similar but not identical to synapses between neurons and can can serve as a model for synapses in general. We have found that a protein called Adducin (Add) is located at the NMJ of the fruit fly. Others have found that this protein is present in synapses in the mammalian brain. Knowledge about the function of this protein at the fruit fly NMJ can help us understand how synapses in the brain work, which could also clarify how memory and learning occur. We have also found that levels of Adducin (called Hts in the fly) can increase or decrease the size of the synaptic branching at the NMJ. This is important as the synaptic branching is likely involved in modifying a 'motor memory', or may serve as a way of changing the efficiency of information transfer from a neuron to a muscle so as to enhance motor performance precision. To understand how Adducin achieves its effects we will see what other proteins it interacts with. We find that Adducin/Hts is closely linked to another protein called Discs large (Dlg), which is similar in structure to an important protein in mammalian synapses called the PSD-95 protein. Interestingly, the Adducin/Hts protein can modify the Dlg protein through the action of several enzymes called protein kinases and we think that Add/Hts is acting through these protein kinases to modify Dlg. In this grant we will explore how much of the effects of Adducin/Hts is mediated by acting on Dlg. We will also explore other ways of how Adducin/Hts may be acting even if its effects are not mediated by Dlg. For instance, Adducin/Hts may be sticking to the membranes of cells and acting as a scaffold to permit binding of the cellular 'skeleton' of actin and spectrin filaments that are important for the structure of the synapse.

神经细胞在称为突触的连接处相互通讯。当神经元连接到肌肉时，连接的突触称为神经肌肉接头（NMJ）。 NMJ 与神经元之间的突触相似但不完全相同，可以作为一般突触的模型。我们发现果蝇的 NMJ 处存在一种名为 Adducin (Add) 的蛋白质。其他人发现这种蛋白质存在于哺乳动物大脑的突触中。了解果蝇 NMJ 中这种蛋白质的功能可以帮助我们了解大脑中的突触如何工作，这也可以阐明记忆和学习是如何发生的。我们还发现内收蛋白（在果蝇中称为 Hts）水平可以增加或减少 NMJ 突触分支的大小。这很重要，因为突触分支可能涉及修改“运动记忆”，或者可以作为改变从神经元到肌肉的信息传输效率的一种方式，从而提高运动表现的精度。为了了解内收蛋白如何实现其作用，我们将了解它与哪些其他蛋白质相互作用。我们发现，Adducin/Hts 与另一种称为 Discs Large (Dlg) 的蛋白质密切相关，该蛋白质在结构上与哺乳动物突触中的一种重要蛋白质 (PSD-95 蛋白质) 相似。有趣的是，Adducin/Hts 蛋白可以通过几种称为蛋白激酶的酶的作用来修饰 Dlg 蛋白，我们认为 Add/Hts 是通过这些蛋白激酶来修饰 Dlg 的。在这笔资助中，我们将探讨内收蛋白/Hts 的作用有多少是通过作用于 Dlg 来介导的。我们还将探索内收蛋白/Hts 如何发挥作用的其他方式，即使其作用不是由 Dlg 介导的。例如，内收蛋白/Hts可能粘附在细胞膜上并充当支架，以允许肌动蛋白和血影蛋白丝的细胞“骨架”结合，这对突触的结构很重要。