C3 Awards Research Grant to Dr. Jaakko Sarparanta to Investigate Relationship Between Calpain 3 Activity and the Protein Titin

Titin is a large protein that functions as a molecular spring in muscle cells. It has recently been shown that calpain 3, the protein that is associated with LGMD2A (a form of calpainopathy), can cut titin, a protein that is associated with several muscle diseases including LGMD2J (a form of titinopathy). However, the physiological importance of this cleavage activity is unknown. Further, the fate of the resulting titin fragments is unclear. Dr. Sarparanta aims to understand the physiological role of calpain 3 in cutting titin and how dysfunction of this activity may lead to muscle disease.

Dr. Sarparanta states that the interplay of titin and calpain 3 is an intriguing topic. Although calpain 3 has been long known to bind titin at several sites, the functions of these multiple interactions are not well understood. Furthermore, the interaction in the M-band of the sarcomere, where the identified titin processing takes place, has not been studied extensively. Importantly, Dr. Sarparanta adds, “We believe this part of titin plays a role in the regulation of calpain 3 in the entire muscle fiber.”

C3 Scientific Director Dr. Jennifer Levy notes, “The biological roles of calpain 3 in muscle are still not fully understood. We are excited to fund Dr. Sarparanta’s project, which will contribute to our knowledge of what calpain 3 does in healthy muscle. A greater understanding of calpain 3’s role in muscle may lead to the identification of new pathways that could be targeted when developing therapies for LGMD2A.”