Red cell membrane polypeptides under normal conditions and in genetic disorders.
Broadly speaking, the red cell membrane is comprised of --a cholesterol-rich phospholipid bilayer that is studded by a large number of trans-bilayer proteins, --of glycosylphosphatidylinositol-anchored proteins (GPI-proteins) standing outside, and --an important protein assembly, the erythrocyte or membrane skeleton, that laminates the inner surface of the bilayer. Among the trans-bilayer proteins, one finds the anion exchanger, the glycophorins, the glucose transporter, a variety of cation transporters and pumps, and of course proteins carrying the epitopes of many blood groups. Among the GPI-proteins, one encounters the acetylcholinesterase and the decay-accelerating factor (CD 55). Among the skeletal proteins, finally, one recognises spectrin, actin (and a number of actin-binding proteins other than spectrin: dematin, tropomyosin, tropomodulin, etc.), protein 4.1 and protein p55. Spectrin heterotetramer organizes into a bidimensional network with a hexagonal mesh on the average. This network is linked to trans-bilayer proteins, through the complex beta-spectrin-ankyrin-anion exchanger (+ protein 4.2) on the one hand and, on the other hand, through the triangular interaction between protein 4.1, glycophorin C and protein p55. The sequence of the above proteins and the exon-intron organisation of their genes are known in most cases. Many proteins have a widespread tissue distribution in the form of variants adapted to their local functions. Such variants may be the products of multigene families (anion exchanger, ankyrin, spectrin), or derive from a single gene (protein 4.1, protein 4.2), the transcripts of which undergo cell-specific alternative splicing. It has been established that many congenital haemolytic anaemias result from mutations altering the above-mentioned genes. We will provide two examples. Hereditary elliptocytosis stems from an array of mutations located at, or near the head-to-head self-association region of two spectrin alpha beta dimers, or from mutations which, most often, yield a reduction (heterozygous state) or the lack (homozygous state) of protein 4.1. The aggravation of elliptocytosis associated with alpha-spectrin mutations frequently yields poikilocytosis and usually stems from the occurrence, in trans, of a low expression allele, allele alpha LELY. Hereditary spherocytosis derives from mutations in the ankyrin gene (80% of the cases), the anion exchanger gene (10-15% of the cases), the protein 4.2 gene (rare cases) and the alpha- and beta-spectrin genes (rare cases). Anion exchanger mutations usually cause the decrease in this protein (heterozygous state).(ABSTRACT TRUNCATED AT 250 WORDS)
Delaunay
J
J
Laboratoire de génétique humaine, CNRS URA 1171, Institut Pasteur de Lyon, France.
D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics; D017487:Ankyrins / Q000235:genetics; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics*; D003598:Cytoskeletal Proteins; D004612:Elliptocytosis, Hereditary / Q000097:blood / Q000235:genetics; D004910:Erythrocyte Membrane / Q000737:chemistry*; D030342:Genetic Diseases, Inborn / Q000097:blood* / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009479:Neuropeptides; D017354:Point Mutation; D013049:Spectrin / Q000235:genetics; D013103:Spherocytosis, Hereditary / Q000097:blood / Q000235:genetics
D001457:Anion Exchange Protein 1, Erythrocyte; D017487:Ankyrins; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1; D013049:Spectrin