Grant: Project Grant

We discovered a family of proteins called the SLMAPs which are residents of the membrane systems of the heart cell. The heart cell membrane and the intracellular membranes are structurally organized in a precise fashion for function. In heart disease the structure of the membranes falls apart. We believe that the SLMAPs proteins work as a "sticky glue" which helps to bind the different membranes together as well as organize protein communication. We are investigating whether these proteins provide the sticky glue that organizes the cell membrane and signaling complexes. Our objective is to find out how these proteins can be targeted to the different membranes in cells and then serve to juxtapose the cell membrane for communication of signals. We have created genetically modified mice where there is either too much SLMAP in the heart or none at all. We propose to use these mice to see the function of SLMAP on the membrane biology of the heart and signals. In addition our data indicates that SLMAPs may translate information from the cell membrane to the genome to regulate gene expression in the heart. Our objective is to understand how changes in membrane biology lead to changes in gene expression and cardiovascular function/disease due to by changes in SLMAP. Mutations in the human SLMAP gene result in the Brugada syndrome (people die suddenly of heart attacks). Our work will lead to a better understanding and lay the foundation for further genetic screening and treatment of not just Brugada patients who suffer fatal arrhythmia but all types of heart disease.