Our long-term goal is to establish how mechanical input is translated into molecular signals. We focus on titin, the largest protein in the human body and the multifunctional coxsackie-adenovirus receptor (CAR).
To lay the groundwork for the in vivo analysis of titin’s multiple signaling, elastic, and adaptor domains, we have generated various titin deficient mice (knock-in and conditional knockout animals) and established a tissue culture system to study titin’s muscle and non-muscle functions. We utilize a combination of cell-biological, biochemical, and genetic tools to establish titin as a stretch sensor converting mechanical into biochemical signals.
Using a comparable loss of function approach we have created a conditional knockout of the coxsackie-adenovirus receptor. With these mice, we have demonstrated that CAR is crucial for embryonic development and determines the electrical properties of the heart.