The red cell membrane is likely the best studied mammalian plasma membrane,
primarily due to easy access to mature red cells and simple purification
of red cell membranes (ghosts). The red cell plasma membrane consists
of a complex mixture of lipids and proteins of which the steady state
composition and organization is well maintained during its life in the
circulation. Many humans carry mutations in the globin genes that determine
the structure of
hemoglobin. Most prevalent are mutations that lead
to disease states such as thalassemia or sickle cell anemia, affecting many
millions of individuals worldwide.
The mature mammalian red blood cell or erythrocyte
is characte-rized by a plasma membrane surrounding a cytosol filled
with hemoglobin, the oxygen transporting protein. The cell does
not contain internal organelles.
Despite the fact that the underlying mutation in these disorders are in
the structural or regulatory genes for globin, the red cells are often
characterized by abnormal membranes. Both in sickle cell anemia and thalassemia,
subpopulations of red cells exist that have an abnormal lipid organization,
|A single point mutation in the globin gene leads
to the formation of sickle hemoglobin. Under low oxygen tension as
found in the venous capillaries, the protein polymerizes giving the
cell its abnormal "sickled" shape, and induces changes in
the plasma membrane.
This exposure has very significant physiologic consequences leading to
imbalance in hemostasis as well as altered cell-cell interactions, and
recognition and removal of these cells, contributing to the anemia. These
abnormalities in membrane organization are related to high levels of apoptosis
or programmed cell death in red cell precursors as well as acquired defects,
during the life of the adult red cell.