A NEW FUNCTION FOR ADDUCIN - CALICIUM CALMODULIN-REGULATED CAPPING OFTHE BARBED ENDS OF ACTIN-FILAMENTS

Adducin is a membrane skeleton protein originally described in human e rythrocytes that promotes the binding of spectrin to actin and also bi nds directly to actin and bundles actin filaments, Adducin is associat ed with regions of cell cell contact in nonerythroid cells, where it i s believed to play a role in regulating the assembly of the spectrin-a ctin membrane skeleton. In this study we demonstrate a novel function for adducin; it completely blocks elongation and depolymerization at t he barbed (fast growing) ends of actin filaments, thus functioning as a barbed end capping protein (K-cap similar to 100 nM). This barbed en d capping activity requires the in tact adducin molecule and is not pr ovided by the NH2-terminal globular head domains alone nor by the COOH -terminal extended tail domains, which were previously shown to contai n the spectrin-actin binding, calmodulin binding, and phosphorylation sites. A novel difference between adducin and other previously describ ed capping proteins is that it is down-regulated by calmodulin in the presence of calcium. The association of stoichio- metric amounts of ad ducin with the short erythrocyte actin filaments in the membrane skele ton indicates that adducin could be the functional barbed end capper i n erythrocytes and play a role in restricting actin filament length, O ur experiments also suggest novel possibilities for calcium regulation of actin filament assembly by adducin in erythrocytes and at cell-cel l contact sites in nonerythroid cells.