An altered calmodulin binding protein in cystic fibrosis--a clue to the biochemical defect

Abstract

Cytosolic extracts prepared from submandibular tissues of CF patients showed a greater ability to activate calmodulin-deficient cyclic AMP phosphodiesterase than did control extracts. Thus, apparent calmodulin levels measured by cyclic AMP phosphodiesterase activation were significantly greater (p less than 0.001) in CF submandibular extracts than control; whereas calmodulin levels measured by radioimmunoassay were not different. In addition a calmodulin-binding protein of molecular weight 61,000 which showed a specific Ca2+-dependent interaction with calmodulin, was shown to be markedly altered in heat-treated extracts from CF submandibular glands. The results indicate that a specific protein which modulates selective biological action(s) of calmodulin is altered in CF. This would provide a biochemical link between disturbances in autonomic function and Ca2+ homeostasis seen in this disease and might therefore be closely related to the genetic defect.