High impact information on Mtm1

• The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice [1].
• Myotubularin is a ubiquitously expressed phosphatase that acts on phosphatidylinositol 3-monophosphate [PI(3)P], a lipid implicated in intracellular vesicle trafficking and autophagy [1].
• Expression of wt myotubularin, although not affecting activation of proximal insulin signal transduction targets such as protein kinase B and MAPK, induced a decrease in insulin-induced glucose uptake, whereas basal glucose uptake was augmented by expression of D278A (DA) and C375S (CS) mutants [2].
• Biochemical and in vivo studies define myotubularin as a phosphatidylinositol 3-phosphate [PtdIns(3)P] phosphatase [2].
• Moreover, overexpression of myotubularin in 3T3-L1 adipocytes impaired insulin-induced translocation at the plasma membrane of green fluorescent protein-tagged glucose transporter 4 [2].

Biological context of Mtm1

• In keeping with its biochemical function, overexpression of wt myotubularin as an enhanced green fluorescent protein fusion disrupted the endosomal punctuated staining of the FYVE (Fab1p/YOTB Vac1p/EEA1)-domain-containing PtdIns(3)P binding protein early endosomal antigen 1 as well as of a gluathione-S-transferase-FYVE probe directed to PtdIns(3)P [2].
• Early and severe presentation of X-linked myotubular myopathy in a girl with skewed X-inactivation [3].
• Truncated L1 elements are located inside introns of many genes and among these genes myotubularin and insulin I are known to regulate cell growth [4].
• Gene expression analyses in X-linked myotubular myopathy [5].

Anatomical context of Mtm1

• Expression of myotubularin by an adenoviral vector demonstrates its function as a phosphatidylinositol 3-phosphate [PtdIns(3)P] phosphatase in muscle cell lines: involvement of PtdIns(3)P in insulin-stimulated glucose transport [2].

Associations of Mtm1 with chemical compounds

• To test this hypothesis, macrophage cellular levels of PtdIns-3-P were altered by retroviral introduction of the type III Phosphoinositide 3-Kinase (VPS34) and the PtdIns-3-P phosphatase myotubularin 1 (MTM1) [6].

Analytical, diagnostic and therapeutic context of Mtm1

• These mutant mice represent animal models for the human disease and will be a valuable tool for understanding the physiological role of myotubularin [1].

References