SPARC: Stim and Plectin mediated Regulation of SERCA

Healthy muscle function - whether in the heart or the limbs - relies on precise control of calcium, an ion that acts like a switch to turn muscle activity on and off. Inside muscle cells, a structure called the sarcoplasmic reticulum (SR) stores and releases calcium as needed. The SR also works closely with mitochondria, the energy powerhouses of the cell, to make sure muscles get the energy they need to work properly. Certain proteins - like desmin, plectin, and one called Stim - help anchor the SR and mitochondria in place and help control how calcium is handled in the muscle. Problems with these proteins can disrupt calcium flow, impair energy production, and are linked to diseases like muscular dystrophy and heart failure. However, how these proteins work together, or how they may differ in various types of muscle or between males and females, is not understood to date. In this project, we will study how these proteins influence calcium control and energy use in muscles. To do this, well use specially bred mice that are missing one or more of these proteins. Well look at different muscle types (like leg muscles and heart muscle), and test how well they manage calcium and produce energy - both at rest and under physical stress. Well do this by using advanced imaging and other techniques to investigate changes in muscle structure and function. Collectively, the proposed research is exploring how named proteins affect muscle calcium homeostasis and energy metabolism. Understanding these processes could lead to new treatments for people with muscle diseases or heart conditions caused by poor calcium regulation and energy use.