Grant: Operating Grant: Fall 2008 Priority Announcement (IMHA)

Mutations to specific structural proteins have been implicated in the development of various muscle disease states such as the Limb-Girdle Muscular Dystrophies (LGMDs). These particular proteins are, however, part of a large protein complex involving other proteins whose structure and function are less well-defined. One of these proteins, Xin, directly interacts with key structural proteins, but its physiological role is largely unknown. We have recently shown a robust increase in Xin expression within injured skeletal muscle, specifically in the muscle stem cells and in newly regenerated muscle fibres. We also highlight the importance of Xin in maintaining muscle stem cell function as repressing Xin expression delays regeneration from damage and reduces the expression of other key structural proteins. In these proposed studies we plan to uncover the roles and regulation of Xin within the muscle stem cell and investigate the effects of altered Xin expression on skeletal muscle function and regenerative capacity. We hypothesize that Xin is necessary for maintaining skeletal muscle integrity and promoting the activation of muscle stem cells during regeneration. Understanding the roles and regulation of Xin, as well as its relationships with other structural proteins, will introduce new insights into the development and progression of the LGMDs and will lead to the advancement of new therapies.