MTM1-MTMR12 interactions in normal and disease states.

<p>Under normal conditions, MTM1 and MTMR12 interact in skeletal muscle and regulate skeletal muscle architecture and function. Loss of function mutations of <i>MTM1</i> (red cross) in skeletal muscle are associated with centronuclear myopathy and with a secondary reduction in MTMR12 levels. In centronuclear myopathy, disease causing missense mutations (red circle) that disrupt interactions between MTM1 and MTMR12 result in decreased stability of myotubularin causing myotubular myopathy associated with reduced levels of MTMR12. Loss of <i>MTMR12</i> in zebrafish and mammalian cells, results in decreased levels of myotubularin resulting in pathological changes similar to centronuclear myopathy.