The myotubularin family: from genetic disease to phosphoinositide metabolism

Abstract

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, dual-specificity protein phosphatases and the lipid phosphatase PTEN. Myotubularin (hMTM1), the founder member, is mutated in myotubular myopathy, and a close homolog (hMTMR2) was recently found mutated in a recessive form of Charcot-Marie-Tooth neuropathy. Although myotubularin was thought to be a dual-specificity protein phosphatase, recent results indicate that it is primarily a lipid phosphatase, acting on phosphatidylinositol 3-monophosphate, and might be involved in the regulation of phosphatidylinositol 3-kinase (PI 3-kinase) pathway and membrane trafficking.