Regulation of myotubularin function by the novel 3-phosphatase adapter protein (3-PAP)

新型 3-磷酸酶接头蛋白 (3-PAP) 对肌管蛋白功能的调节

• 批准号: nhmrc : 400080
• 负责人: Prof Christina Mitchell
• 金额: $ 32.56万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/regulation-myotubularin-function-3-pap/96136
• 关键词: Regulation; myotubularin; function; novel; phosphatase

Phospholipids are important components of cell membranes. Phospholipids are turned-on by enzymes called kinases and these phospholipids stimulate a variety of critical functions within the cells. Phospholipids are turned-off by another type of enzymes classed as phosphatases, thereby switching off a broad range of cell functions. Myotubularin is an enzyme, which neutralizes particular type of phospholipids that are involved in the shuttling of proteins between compartments within the cell. Loss of function of myotubularin, due to inherited genetic changes (mutations), leads to abnormal muscle development manifesting as weakness since birth, and this particular disease is known as 'X-linked myotubular myopathy'. However, there is yet no information on the mechanisms by which failure of protein shuttling (transport) causes myopathy. We have discovered a new protein, 3-phosphatase adapter protein (3-PAP) that links with myotubularin and plays an important role in the function of myotubularin. Our research proposal seeks to clarify the important role of 3-PAP in the development of muscle cells. We propose to study the location of 3-PAP within cells and analyse the influence of 3-PAP on protein shuttling. We have created mice that are deficient in the 3-PAP gene. These special mice will help us understand the importance of 3-PAP in the development and function of nerve and muscle tissue.

磷脂是细胞膜的重要组成部分。磷脂被称为激酶的酶转基因，这些磷脂刺激细胞内的各种关键功能。磷脂被另一种类型的酶归类为磷酸酶，从而关闭了广泛的细胞功能。肌管蛋白是一种酶，它可以中和特定类型的磷脂，这些磷脂与细胞内隔室之间的蛋白质穿梭有关。由于遗传遗传变化（突变），肌管蛋白的功能丧失导致异常的肌肉发育表现为自出生以来的弱点，这种特殊疾病被称为“ X连接的肌管肌病”。但是，目前尚无有关蛋白质穿梭（运输）失败导致肌病的机制的信息。我们发现了一种新的蛋白质3-磷酸酶衔接蛋白（3-PAP），该蛋白与肌管蛋白联系在一起，并在肌管蛋白的功能中起重要作用。我们的研究建议旨在阐明3-PAP在肌肉细胞发展中的重要作用。我们建议研究3-PAP在细胞中的位置，并分析3-PAP对蛋白质穿梭的影响。我们创建了缺乏3-PAP基因的小鼠。这些特殊的小鼠将帮助我们了解3-PAP在神经和肌肉组织的发育和功能中的重要性。