Myotubularins

Begley M.J., Taylor G.S., Brock M.A., Ghosh P., Woods V.L. Jr, Dixon J.E. Molecular basis for substrate recognition by MTMR2, a myotubularin family phosphoinositide phosphatase. Proc. Natl Acad. Sci. USA 2006, 103, 927-932. 

Blondeau, E Laporte, J. Bodin, S. Superti-Furga, G. Payrastre, B. Man-del, J.-L. Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway. Hum. Mol. Genet., 9, 2223-2229 (2000)... 

Tronchere, H., Buj-Bello, A., Mandel, J.L., and Payrastre, B., 2003, Implication of phosphoinositide phosphatases in genetic diseases The case of myotubularin. Cell Mol. Life Sci. 60 2084-2099. 

Berger, P., Bonneick, S., Willi, S., Wymann, M., and Suter, U., 2002, Loss of phosphatase activity in myotubularin-related protein 2 is associated with Charcot-Marie-Tooth disease type 4B1. Hum. Mol. Genet. 11 1569-1579. 

Buj-Bello, A., Laugel, V, Messaddeq, N., Zahreddine, H., Laporte, J., Pellissier, J.F., and Mandel, J.L., 2002, The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but... 

Maehama, T., Taylor, G.S., and Dixon, J.E., 2001, PTEN and myotubularin Novel phosphoinositide phosphatases. Annu. Rev. Biochem. 70 247-279. 

Tsujita, K., Itoh, T., Ijuin, T., Yamamoto, A., Shisheva, A., Laporte, J., and Takenawa, T., 2004, Myotubularin regulates the function of the late endosome through the gram domain-phosphatidylinositol 3,5-bisphosphate interaction. J Biol. Chem. 279 13817-13824. 

Phosphatidylinositol 5-phosphate (PI-5-P, 4) is formed by the hydrolysis of 3-phosphate from PI-3.5-P2 by myotubularin,... 

The earlier predicted myotubularin-related phosphatase MTMR15 (Alonso et al., 2004, Cell, 117, 699-711) is not included here. The protein (KIAA1018/FAN1) was identified as a DNA repair... 

Formerly DUPDl, but does not contain an N-terminal cyclophilin domain, as originally annotated. The mouse ortholog also lacks cyclophilin domain. Thus, the name DUPDl is a misnomer hjumpy lacks any of the typical domains characteristic of the myotubularin family, but it does contain the myotubularin-specif WDR motif within the P loop and does have phosphatidylinositol-... 

Bolino A, MugUa M, Conforti FL et al (2000) Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Nat Genet 25 17-19... 

Wishart. M.. and J. Dixon. 2002. PTEN and myotubularin phosphatases from 3-phosphoinositide dephosphorylation to disease. Trends Cell. Biol. 12 579-584. 

Figure 3. Pathways of phosphoinositide synthesis and interconversions. The figure shows the main pathways of phosphoinositide synthesis in mammalian cells. For the sake of clarity only the enzymatic activities (3-, 4- or 5-kinases or phosphatases) are indicated. In some cases the identification of key enzymes is mentioned (class I, II and III PI 3-kinases, PTEN, MTM, MTMR or SHIP). PI3K, phosphoinositide 3-kinase. PTEN, phosphatase and tensin homolog deleted on chromosome ten. MTM, myotubularin. MTMR, myotubular myopathy-related protein. SHIP, Src homology 2-containing inositol 5-phosphatase. PLC, phospholipase C. DAG, diacylglycerol.

The gene mutated in X-linked myotubular myopathy (XLMTM), a severe congenital disorder characterized by generalized muscle weakness and hypotonia, codes for a ubiquitously expressed protein, myotubularin. This protein presents the conserved sequence of the phosphotyrosine phosphatase s active site. However, studies of its substrate specificity have shown that myotubularin s preferred substrates are PtdIns(3)P and Ptdlns(3,5)P2 (Blondeau et al, 2000 Schaletzky et al, 2003). Accordingly, it has been shown that... 

Kim, SA, Taylor, GS, Torgersen, KM and Dixon, JE (2002) Myotubularin and MTMR2, phosphatidylinositol 3-phosphatases mutated in myotubular myopathy and type 4 B Char-cot-Marie-Thooth disease. J Biol Chem, 211, 4526-4531. 

Schaletzky, J, Dove, SK, Short, B, Lorenzo, O, Clague, MJ and Barr, FA (2003) Phosphatidylinositol-5-phosphate activation and conserved substrate specificity of the myotubularin phosphatidylinositol 3-phosphatases. Curr Biol, 13, 504-509. 

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