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The Red Cell

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
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.
hemoglobin. Most prevalent are mutations that lead to disease states such as thalassemia or sickle cell anemia, affecting many millions of individuals worldwide.

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, exposing phosphatidylserine.

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.

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