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。磷脂是由一种叫做激酶的酶激活的，这些磷脂刺激细胞内的各种关键功能。磷脂被另一种被归类为磷酸酶的酶关闭，从而关闭了广泛的细胞功能。肌管蛋白是一种酶，它能中和细胞内特定类型的磷脂，这些磷脂参与了细胞内不同区室之间蛋白质的穿梭。由于遗传基因改变（突变）导致肌小管蛋白功能丧失，导致肌肉发育异常，从出生起就表现为虚弱，这种特殊疾病被称为“x连锁肌小管肌病”。然而，关于蛋白质穿梭（运输）失败导致肌病的机制还没有信息。我们发现了一种新的蛋白，3-磷酸酶连接蛋白（3-phosphatase adapter protein, 3-PAP），它与肌小管蛋白连接，在肌小管蛋白的功能中起重要作用。我们的研究计划旨在阐明3-PAP在肌肉细胞发育中的重要作用。我们建议研究3-PAP在细胞内的位置，并分析3-PAP对蛋白穿梭的影响。我们创造了缺乏3-PAP基因的老鼠。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。