PH domain에 의한 myotubularin-related (MTMR)2 phosphatidylinositol phosphatase의 조절

Abstract

Regulation of myotubularin-related (MTMR)2 phosphatidylinositol phosphatase by PH domain

Lee, Won-Hak Advisor : Prof. Yoon Jung-Hoon, DDS, Ph.D. Department of Dentistry, Graduate School of Chosun University

The myotubularin (MTM) family constitutes one of the most highly conserved protein-tyrosine phosphatase subfamilies in eukaryotes. MTM1, the archetypal member of this family, is mutated in X-linked myotubular myopathy, whereas mutations in the MTM related (MTMR)2 gene cause the type 4B Charcot-Marie-Tooth disease, a severe hereditary motor and sensory neuropathy. In this study, we investigated the role of pleckstrin homology (PH) domain of MTMR2. We demonstrate here that the PH domain of MTMR2 directly interacts with phosphatidylinositol (PtdIns)(3)P, PtdIns(5)P, and to a lesser extent PtdIns(4)P. Furthermore, MTMR2-PH domain is required for targeting MTMR2 to the cytoplasmic compartment. Mutation in the PH domain abolished its phospholipid binding ability and MTMR2 subcellular localization. These results suggest that the PH domain regulates MTMR2 localization and function through its interaction with phosphoinositides and give us the clue to understand the pathogenic effect of PH domain. Key words : phosphoinositides, PH domain, MTMR2, Charcot-Marie-Tooth disease