Red blood cells, erythrocytes, are biconcave, rigid and lacking in a nucleus or other nuclear-derived organelles, such as endoplasmic reticulum or Golgi apparatus. They are initially produced as reticulocytes that continue to synthesize hemoglobin using energy from mitochondria. Eventually protein synthesis ceases, mitochondria no longer function and the mature, red blood cell passively carries oxygen for several months.
Messenger RNA is Transported to Place of Use
Nucleic acids and proteins are too large to be moved significantly by diffusion within a cell. Proteins are typically translated on ribosomes in the region of the cell where they will be used. In the case of red blood cells, their major proteins, the alpha and beta globins of hemoglobin and membrane scaffolding proteins, such as spectrin and actin, are translated on ribosomes next to the cytoplasmic membrane. The mRNAs for these proteins were transcribed from their genes in the nucleus and then transported to the cytoplasmic membrane for translation.
Reticulocytes Named for Web of mRNA and Ribosomes
Red blood cells develop in the bone marrow, where stem cells divide to produce the precursors of all of the blood cells. Some of these stem cells respond to a hormone, erythropoeitin, express genes for hemoglobin and the cytoskeletal proteins of RBCs and move mRNA for these proteins to the underside of the cytoplasmic membrane. Ribosomes attach in long decorated necklaces along the mRNAs as they translate the genetic code of the mRNAs into corresponding proteins. It is this web of mRNA and ribosomes attached to the cytoplasmic membrane that ultimately provides the unique staining characteristics of the reticulocyte.
The RBC Cytoskeleton Forms the Reticulocyte
The scaffolding proteins spontaneously assemble into a structure that defines the surface area of the newly forming reticulocyte, as the nucleus, with its own coating of cytoplasmic membrane pinches off. The reduced volume and rigid surface makes the reticulocyte a disk with two concave faces. Since the nucleus is the source of the secretory organs, e.g. endoplasmic reticulum, Golgi apparatus, lysosomes, etc., then the reticulocyte lacks all of these structures and contains only cytoplasmic enzymes, e.g. glycolysis, and a few mitochondria. The nucleus also supplies most of the proteins that are needed for mitochondrial function, so the remaining mitochondria also stop functioning.
Hemoglobin Synthesis Continues as RBCs Mature
The only remaining mRNA in the reticulocyte is the large amount of alpha and beta globin that continue to be translated into protein by the cytoplasmic enzymes that supply the amino acids that are strung together by ribosomes. After a few days, the mature RBC has formed and the reticular pattern of mRNA and ribosomes disappears. The mature RBC circulates in the blood for three to four months. The discoid shape of the RBC helps them to pass through tight capillaries and if they are twisted the RBCs release chemicals that cause tight capillaries to briefly flare open.
Mature RBCs Carry Oxygen Bound to Hemoglobin
Hemoglobin proteins (two alpha and two beta) form a complex so that each of the four globin proteins has its own iron held on a plate-like heme structure. The beauty of this arrangement is that in the presence of a high concentration of oxygen, as in the lung, the hemoglobin complex load all of the heme groups with oxygens. As the RBCs travel through tissue capillaries and the oxygen level plummets, then all of the heme groups lose their oxygen at once, so that the depleted hemoglobin complexes can return to the lungs empty.
Aged RBCs Are Recycled
Eventually the RBCs are unable to spring back into shape as they pass through capillaries and this lack of flexibility traps old RBCs in the spleen. The damaged RBCs are phagocytosed by macrophages, the proteins are hydrolyzed, iron is concentrated in transferrin and the chemical frame of the heme structure is partially disassembled and ultimately eliminated as part of the bile used in digestion. Millions of RBCs are born and recycled each day to maintain a constant level of oxygen in tissues.
References:
Alberts, B. et al. 2008. Molecular Biology of the Cell, 5th ed., Garland Science.
Campbell, N.E, et al. 2007. Biology, 8th ed., Benjamin Cummings.
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