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

磷脂是细胞膜的重要组成部分。磷脂是由一种称为激酶的酶激活的，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，它中和特定类型的磷脂，这些磷脂参与蛋白质在细胞内的隔间之间的穿梭。由于遗传基因改变(突变)导致的肌管蛋白功能丧失，导致肌肉发育异常，从出生起就表现为虚弱，这种特殊的疾病被称为X连锁肌管性肌病。然而，目前还没有关于蛋白质穿梭(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，3-磷酸酶适配蛋白(3-PAP)，它与肌管蛋白相连，在肌管蛋白的功能中发挥着重要作用。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在细胞内的定位，并分析3-PAP对蛋白质穿梭的影响。我们创造了3-PAP基因缺陷的小鼠。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。

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.