Alphaadducin

Alpha-adducin, encoded by the ADD1 gene in humans, is a cytoskeletal protein that is a member of the adducin family. Adducins form heterotetramers of two alpha subunits and two beta or gamma subunits, and alpha-adducin often pairs with beta- or gamma-adducin to create functional complexes. In red blood cells, alpha-adducin participates in capping the fast-growing end of actin filaments and in promoting the assembly of the spectrin–actin membrane skeleton, helping to stabilize the plasma membrane during deformation. The protein is also expressed in other tissues, including the kidney and brain, where it is thought to contribute to cell shape, membrane stability, and possibly junctional organization.

Alpha-adducin activity is regulated by calcium/calmodulin and phosphorylation. Binding of Ca2+/calmodulin modulates its actin-capping activity, and phosphorylation by protein kinase C reduces its association with the cytoskeleton, allowing remodeling of the membrane skeleton during signaling events.

Genetic variation in ADD1 has been linked to blood pressure regulation and salt sensitivity in some populations. The most studied polymorphism is G460W, which has been associated with altered sodium handling and modestly increased risk of essential hypertension in certain studies, with results varying by ethnicity. Some research suggests an influence on response to thiazide diuretics, illustrating a potential pharmacogenetic role, though conclusions are not uniform across populations.

Beyond hypertension, alpha-adducin is examined for its role in membrane-cytoskeleton dynamics in nonerythroid cells, contributing to understanding of cell morphology and mechanotransduction. Further research continues to define its tissue distribution, interacting partners, and clinical relevance.