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Figure 164-1 The erythrocyte membrane. A model of the major proteins of the erythrocyte
membrane
Membrane Lipids
Red cell membrane lipids are asymmetrically distributed across the
bilayer membrane, reflecting a steady state involving a constant
exchange of phospholipids between the two bilayer hemileaflets.
Membrane Proteins
The red cell membrane contains about a dozen major proteins and
hundreds of minor ones. Membrane proteins are classified as integral,
penetrating or crossing the lipid bilayer and interacting with the
hydrophobic lipid core, or peripheral, interacting with integral proteins
or lipids at the membrane surface but not penetrating into the bilayer
core. Integral membrane proteins include the glycophorins, the Rh
proteins, Kell and Duffy antigens, and transport proteins such as band
3 (AE1, anion exchanger 1, SLC4A1), Na+, K+-ATPase, Ca2+-ATPase, and
Mg2+-ATPase. Numerous membrane receptors and antigens are
present on integral membrane proteins. Peripheral membrane
proteins are on the cytoplasmic membrane face and include enzymes
such as glyceraldehyde 3-phosphate dehydrogenase and the structural
proteins of the spectrin-actinbased membrane skeleton.
Band 3, the major integral protein of the red cell, has two primary
functions: ion transport and maintenance of protein-protein
interactions. Band 3 mediates chloride-bicarbonate exchange and
provides a binding site for glycolytic enzymes, hemoglobin, and the
skeletal proteins ankyrin, protein 4.1, and protein 4.2. A single Nglycan chain attached to an Asn in the membrane spanning domain of
band 3 is composed of N-acetyl-D-lactosamine units arranged in an
unbranched, linear fashion in fetal erythrocytes (i antigen) and in a
branched fashion in adult cells (I antigen).
The glycophorins are the next most abundant family of integral
membrane proteins. They provide most of the negative surface charge
required by red cells to avoid sticking to each other and to the vascular
wall. They are involved in transmembrane signaling and carry
receptors for Plasmodium falciparum, a number of viruses and bacteria,
and several blood group antigens. Other integral proteins include the
Rh proteins, Kell antigen, the glucose transporter, the urea
transporter, Na+, K+-ATPase, Ca2+-ATPase, Mg2+-ATPase, various
kinases and phosphatases, acetylcholinesterase, decay accelerating
factor, complement proteins, and receptors for transferrin, insulin,
insulin-like growth factors, thyroid hormone, parathyroid hormone, adrenergic agonists, cholinergic agents, diphtheria toxin,
ceruloplasmin, and opiates.