Palmitoylation of Exocytic Proteins: Role in Membrane Compartmentalization, Intracellular Trafficking, and Function

某些细胞含有小囊或“囊泡”，里面充满了重要的物质，如激素或神经递质。适当的刺激会触发这些小泡与细胞膜的融合，导致细胞分泌货物。膜融合需要大量的蛋白质，确定这些不同的蛋白质是如何调节的是至关重要的。有趣的是，我们已经证明，棕榈酸酯(一种脂肪酸)与某些蛋白质的结合改变了它们在细胞膜上的定位，并调节了它们支持膜融合的能力。这一建议将准确地确定棕榈酸酯添加如何调节介导膜融合的蛋白质的活性，并确定动态添加/移除棕榈酸酯是否对融合活性重要。此外，我们将确定棕榈酸如何调节蛋白质在细胞中特定位置的分类。这些分析将为棕榈酸对膜融合的调控提供有价值的新信息，也将成为理解棕榈酸如何总体上调节蛋白质的分类和膜分布的重要范例。这项研究产生的结果有望有助于癫痫和其他大脑疾病以及糖尿病等代谢疾病的治疗设计。

Certain cells contain small sacs or ‘vesicles‘ filled with important cargo, such as hormones or neurotransmitters. Appropriate stimuli trigger the fusion of these vesicles with the cell membrane, resulting in cargo secretion from the cell. A large number of proteins are required for membrane fusion, and it is essential to determine how these various proteins are regulated. Interestingly, we have shown that the attachment of palmitate (a fatty acid) to certain proteins modifies their localisation in the cell membrane and regulates their ability to support membrane fusion. This proposal will precisely determine how palmitate addition regulates the activity of proteins that mediate membrane fusion, and identify whether dynamic addition/removal of palmitate is important for fusion activity. Furthermore, we will determine how palmitate regulates the sorting of proteins to specific locations in the cell. These analyses will provide valuable and novel information on the regulation of membrane fusion by palmitate, and will also serve as an important paradigm to understand how palmitate regulates the sorting and membrane distribution of proteins in general. The results generated from this study will hopefully contribute to the design of treatments for conditions such as epilepsy and other brain disorders, and metabolic disorders such as diabetes.