Regulation of MTMR2 by the inactive phosphatase MTMR13

无活性磷酸酶 MTMR13 对 MTMR2 的调节

• 批准号: 6837925
• 负责人: FRED L ROBINSON
• 金额: $ 4.73万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6837925
• 关键词: Schwann cells; animal tissue; cell line; enzyme complex; enzyme induction /repression; gene expression; hereditary motor and sensory neuropathy; laboratory rabbit; laboratory rat; myelination; neurogenetics; peripheral nervous system; phosphatidylinositols; postdoctoral investigator; protein localization; protein protein interaction; protein structure function; protein tyrosine phosphatase

DESCRIPTION (provided by applicant): Myotubularin related protein 2 (MTMR2) is a phospho-lipid phosphatase specific for the 3 positions of PI(3)P and Pl(3,5)P2. Loss of function mutations in MTMR2 cause the demyelinating peripheral neuropathy Charcot-Maire-Tooth disease type 4B (CMT-4B), a severely debilitating, hereditary condition characterized by focally folded myelin sheaths. Recessive mutations in a second myotubularin family member, MTMR13 (also called SET domain binding factor 2 [SBF2]) also cause CMT-4B. MTMR13 is a catalytically inactive member of the myotubularin inositol lipid phosphatase family. Recent data from our laboratory indicate that MTMR2 also binds to and is regulated by the closely related protein MTMR5 (also called SBF1). MTMR5 is 59% identical to MTMR13, has an identical domain composition, and is also an inactive phosphatase. However, MTMR5 is unlikely to be involved in CMT-4B. We propose to investigate how the lipid phosphatase activity of MTMR2 is regulated. Specifically, the effect of MTMR13 on MTMR2 function will be examined. Initial experiments will involve investigating whether the MTMR2 and MTMR13 proteins physically interact. The effect of MTMR13 association on the catalytic activity of MTMR2 will be analyzed both in vitro and in cell biological experiments. The effect of MTMR2-MTMR13 interactions on the cellular localization of both proteins will also be investigated. Finally, experiments are proposed to identify additional proteins that associate with MTMR13 and MTMR2.

描述（由申请人提供）：肌管蛋白相关蛋白2 （MTMR2）是一种磷脂脂磷酸酶，特异于PI(3)P和Pl(3,5)P2的3个位置。MTMR2的功能突变缺失导致脱髓鞘周围神经病变4B型（CMT-4B），这是一种严重衰弱的遗传性疾病，以局部髓鞘折叠为特征。另一个肌小管蛋白家族成员MTMR13（也称为SET结构域结合因子2 [SBF2]）的隐性突变也会导致CMT-4B。MTMR13是肌管蛋白肌醇脂质磷酸酶家族的催化无活性成员。我们实验室最近的数据表明，MTMR2也与密切相关的蛋白MTMR5（也称为SBF1）结合并受其调节。MTMR5与MTMR13相同59%，具有相同的结构域组成，也是一种无活性的磷酸酶。然而，MTMR5不太可能参与CMT-4B。我们建议研究MTMR2的脂质磷酸酶活性是如何被调节的。具体来说，我们将研究MTMR13对MTMR2功能的影响。最初的实验将包括研究MTMR2和MTMR13蛋白是否物理相互作用。我们将在体外和细胞生物学实验中分析MTMR13结合对MTMR2催化活性的影响。MTMR2-MTMR13相互作用对两种蛋白的细胞定位的影响也将被研究。最后，我们提出了鉴定与MTMR13和MTMR2相关的其他蛋白的实验。