Deleting titin's I-band/A-band junction reveals critical roles for titin in biomechanical sensing and cardiac function.

ABSTRACT: Titin, the largest protein known, forms a giant filament in muscle where it spans the half sarcomere from Z disk to M band. Here we genetically targeted a stretch of 14 immunoglobulin-like and fibronectin type 3 domains that comprises the I-band/A-band (IA) junction and obtained a viable mouse model. Super-resolution optical microscopy (structured illumination microscopy, SIM) and electron microscopy were used to study the thick filament length and titin's molecular elasticity. SIM showed that the IA junction functionally belongs to the relatively stiff A-band region of titin. The stiffness of A-band titin was found to be high, relative to that of I-band titin (∼ 40-fold higher) but low, relative to that of the myosin-based thick filament (∼ 70-fold lower). Sarcomere stretch therefore resu

SUBMITTER: Granzier HL 

PROVIDER: S-EPMC4210014 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature