Myotubularin MTM1 Involved in Centronuclear Myopathy and its Roles in Human and Yeast Cells

TL;DR

This paper reviews the role of the MTM1 gene and its yeast homolog in centronuclear myopathy, highlighting recent models and understanding of its cellular functions and domains.

Contribution

It provides a comprehensive overview of MTM1's functions, disease involvement, and insights gained from various models including yeast, mice, dogs, and zebrafish.

Findings

MTM1 mutations cause X-linked centronuclear myopathy.

Models like knockout mice and yeast help study MTM1 functions.

MTM1's conserved domains are crucial for its cellular role.

Abstract

Mutations in the MTM1 gene, encoding the phosphoinositide phosphatase myotubularin, are responsible for the X-linked centronuclear myopathy (XLCNM) or X-linked myotubular myopathy (XLMTM). The MTM1 gene was first identified in 1996 and its function as a PtdIns3P and PtdIns(,5)P2 phosphatase was discovered in 2000. In recent years, very important progress has been made to set up good models to study MTM1 and the XLCNM disease such as knockout or knockin mice, the Labrador Retriever dog, the zebrafish and the yeast Saccharomyces cerevisiae. These helped to better understand the cellular function of MTM1 and of its four conserved domains: PH-GRAM (Pleckstrin Homology-Glucosyltransferase, Rab-like GTPase Activator and Myotubularin), RID (Rac1-Induced recruitment Domain), PTP/DSP (Protein Tyrosine Phosphatase/Dual-Specificity Phosphatase) and SID (SET-protein Interaction Domain). This review presents the cellular function of human myotubularin MTM1 and its yeast homolog yeast protein Ymr1, and the role of MTM1 in the centronuclear myopathy (CNM) disease.