Calpastatin overexpression 293T lysate (whole cell)

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

Calpastatin is an endogenous inhibitor of calpain proteases with popular alternate names including CAST. The mass of calpastatin is approximately 70 kDa. It is expressed in various tissues throughout the body such as the brain heart and muscle. Calpastatin regulates the activity of the calpain family of cysteine proteases by binding to their catalytic domains. By modulating calpain activity calpastatin plays a role in several cellular processes including cytoskeletal remodeling and signal transduction.

Biological function summary

Calpastatin regulates intracellular protein degradation by inhibiting calpain activity. This inhibition prevents uncontrolled proteolysis of specific substrate proteins. Calpastatin is not part of a larger protein complex but interacts independently with multiple isoforms of calpain. It helps maintain cellular homeostasis by influencing autophagy apoptosis and cell migration integrating signals that drive various physiological processes.

Pathways

Calpain activity modulation through calpastatin takes place in several key biological pathways including apoptosis and the Wnt signaling pathway. Calpain-mediated cleavage affects cell survival and death by modifying Bcl-2 family proteins. In the Wnt signaling pathway calpastatin regulates calpain which influences β-catenin degradation therefore affecting cell proliferation and differentiation pathways. These interactions highlight calpastatin’s central role in managing fundamental cellular events.

Uncontrolled calpain activity due to insufficient calpastatin levels relates to neurodegenerative diseases such as Alzheimer's disease and muscular dystrophies. In Alzheimer's disease reduced calpastatin levels may lead to excessive calpain activity resulting in tau protein hyperphosphorylation and neurofibrillary tangles. Calpastatin-related calpain dysregulation also contributes to muscle cell degeneration seen in muscular dystrophies by affecting structural proteins like dystrophin. These connections highlight the critical balance that calpastatin maintains in cellular processes pertinent to human health.