In the red blood cell (RBC),
adducin is present primarily as tetramers of alpha- and beta-subunits at
spectrin-actin junctions, or junctional complexes. Mouse RBCs also contain small amounts of
gamma-adducin. Platelets contain alpha- and
gamma-adducin only.
Adducin functions as a barbed-end
actin capping protein to regulate actin filament length and recruits
spectrin to the ends of actin filaments. To further define
adducin's role in vivo, we generated
alpha-adducin knockout mice.
alpha-Adducin is absent in all tissues examined in homozygous null mice. In RBCs, beta- and
gamma-adducin are also absent, indicating that
alpha-adducin is the limiting subunit in tetramer formation at the
spectrin-actin junction. Similarly,
gamma-adducin is absent in alpha-null platelets.
alpha-Adducin-null mice display compensated
hemolytic anemia with features characteristic of RBCs in
hereditary spherocytosis (HS), including spherocytes with significant loss of surface area, decreased mean corpuscular volume (MCV), cell
dehydration, and increased osmotic fragility. Platelets maintain their normal discoid shape, and bleeding times are normal.
alpha-Adducin-null mice show growth retardation at birth and throughout adulthood. Approximately 50% develop lethal
communicating hydrocephalus with striking dilation of the lateral, third, and fourth ventricles. These data indicate that
adducin plays a role in RBC membrane stability and in cerebrospinal fluid homeostasis.