The myotubularin family: from genetic disease to phosphoinositide metabolism

The myotubularin-related genes define a large family of eukaryotic proteins , most of them initially characterized by the presence of a ten-amino acid consensus sequence related to the active sites of tyrosine phosphatases, du al-specificity protein phosphatases and the lipid phosphatase PTEN. Myotubu larin (hMTM1), the founder member, is mutated in myotubular myopathy, and a close homolog (hMTMR2) was recently found mutated in a recessive form of C harcot-Marie-Tooth neuropathy. Although myotubularin was thought to be a du al-specificity protein phosphatase, recent results indicate that it is prim arily a lipid phosphatase, acting on phosphatidylinositol 3-monophosphate, and might be involved in the regulation of phosphatidylinositol 3-kinase (P I 3-kinase) pathway and membrane trafficking.