Membrane skeleton

Bennett, V., 1985. The membrane skeleton of human erydirocytes and its implications for more complex cells. Annual Review of Biochemistry 54 273-304. 

Marches , V. T, 1984. Structure and function of die erydirocyte membrane skeleton. Progress in Clinical Biology Research 159 1 — 12. 

Ankyrin deficiency, amounting to a reduction of approximately 50%, has been found in some patients with the dominant type of HS. A primary defect in ankyrin almost certainly reduces the assembly of spectrin into the membrane skeleton of the red blood cell (Davies and Lux, 1989). 

Bennett, V. (1989). The spectrin-actin junction of erythrocyte membrane skeletons. Biochim. Biophys. Acta 988, 107-121. 

Adapted from Lux DE, Becker PS Disorders of the red cell membrane skeleton hereditary spherocytosis and hereditary elliptocytosis. Chapter 95 in The Metabolic Basis of Inherited Disease, 6th ed. Scriver CR et al (editors). McGraw-Hill, 1989. 

Beck, K. A. and Nelson, I. The spectrin-based membrane skeleton as a membrane protein-sorting machine. Am.. Physiol. 270 C1263-C1270,1996. 

What is the function of the membrane skeleton There is a group of hereditary diseases including spherocytosis in which erythrocytes do not maintain their biconcave disc shape but become spherical or have other abnormal shapes and are extremely fragile.269 272 Causes of spherocytosis include defective formation of spectrin tetramers and defective association of spectrin with ankyrin or the band 4.1 protein.265 273 Thus, the principal functions of these proteins in erythrocytes may be to strengthen the membrane and to preserve the characteristic shape of erythrocytes during their 120-day lifetime in the bloodstream. In other cells the spectrins are able to interact with microtubules, which are absent from erythrocytes, and to microtubule-associated proteins of the cytoskeleton (Chapter 7, Section F).270 In nerve terminals a protein similar to erythrocyte protein 4.1 may be involved in transmitter release.274 The cytoskeleton is also actively involved in transmembrane signaling. 

Related proteins occur in other tissues.488 The 911-residue band 3 protein consists of two distinct parts of nearly equal size. The N-terminal portion is attached to the membrane skeleton (Fig. 8-16). The C-terminal part, which is embedded in the membrane, is thought to form 14 transmembrane helices and to contain the ion exchange channel or channels.4893 As previously mentioned, defects in the N-terminal portion cause spherocytosis. The mutation Arg 589 His in the C-terminal half causes renal tubular acidosis in which the kidneys do not adequately remove acids from the body.238 489 Band 3 proteins can also exchange phosphate, sulfate, and phosphoenolpyruvate for Cl or bicarbonate. 

The structure of spectrin and the location of spectrin in the cytoskeleton. (a) An a/3 dimer of spectrin. Both a and f3 subunits are extended structures consisting of end-to-end domains of 106 amino-acyl residues folded into three a helices the subunits twist about one another loosely as shown. (b) The erythrocyte membrane skeleton. Spectrin tetramers ((X2P2), shown in yellow, are linked to the cytoplasmic domain of the anion channel (blue) by the protein ankyrin (red), and to glycophorin and actin filaments by protein 4.1. This structure lends stability to the red cell membrane while maintaining sufficient flexibility to allow erythrocytes to withstand substantial shear forces in the peripheral circulation. 

The membrane skeleton acts as an elastic semisolid, allowing brief periods of deformation followed by reestablishment of the original cell shape (reviewed by Bennett and Gilligan, 1993). Erythrocytes in the human bloodstream have to squeeze repeatedly through narrow capillaries of diameters smaller than their own dimensions while resisting rupture. A functional erythrocyte membrane is pivotal to maintaining the functional properties of the erythrocyte. This importance is apparent when examination is made of many hemolytic anemias, where mutation of proteins involved in the structure of the submembranous cytoskeleton, and its attachment to the lipid bilayer, result in a malformed or altered cytoskeletal architecture and a disease phenotype. 

The primary biochemical defects of HS are linked to proteins important to the interaction between the membrane skeleton and the lipid bilayer involving a- and /3-spectrin, ankyrin, band 3, and protein 4.2 (Gallagher and Forget, 1998). Combined spectrin and ankyrin deficiency (Coetzer et al, 1988 Pekrun et al, 1993 Sawides et al., 1993) is most commonly observed, followed by band 3 deficiency (Iolascon et al, 1992 Jarolim et al,... 

Bennett, V., and Gilligan, D. M. (1993). The spectrin-based membrane skeleton and micron-scale organization of the plasma membrane. Annu. Rev. Cell Biol. 9, 27-66. 

Earnest, J. P., Santos, G. F., Zuerbig, S., and Fox, J. E. (1995). Dystrophin-related protein in the platelet membrane skeleton. Integrin-induced change in detergent-insolubility and cleavage by calpain in aggregating platelets. J. Biol. Chem. 270, 27259-27265. 

Ervasti, J. M., and Campbell, K. P. (1993a). Dystrophin and the membrane skeleton. Curr. Opin. Cell Biol. 5, 82—87. 

Hanspal, M., and Palek, J. (1992). Biogenesis of normal and abnormal red blood cell membrane skeleton. Semin. Hematol. 29, 305-319. 

Jarolim, P., Lahav, M., Liu, S. C., and Palek, J. (1990). Effect of hemoglobin oxidation products on the stability of red cell membrane skeletons and the associations of skeletal proteins Correlation with a release of hemin. Blood 76, 2125-2131. 

Williams, M. W., and Bloch, R. J. (1999). Extensive but coordinated reorganization of the membrane skeleton in myofibers of dystrophic (mdx) mice. J. Cell Biol. 144, 1259-1270. 

Bobrowska-Hagerstrand M, Hagerstrand H, Iglic A. Membrane skeleton and red blood cell vesiculation at low pH. Biochim Biophys Acta 1998 1371(1) 123—128. 

Figure 6-3. Structure of the red cell membrane (a) and the hexagonal lattice structure of the membrane skeleton ( ).

The major components of the membrane skeleton are spectrin, actin, and protein 4.1. Spectrin is a highly flexible, rodlike molecule composed of two nonidentical polypeptides a-spectrin and (3-spectrin.These chains are aligned side by side in the form of a a(3-heterodimer, and spectrin heterodimers in turn join head to head to form (aP)2-tetramers. The tail ends of spec-... 

Band 4.1 Protein 4.1 80 K P Membrane skeleton association with GPC... 

Describe the structural organization of the membrane skeleton that is a major determinant of red cell shape and deforma-bility. 

The breakdown or disorganization of the membrane skeleton can be followed by the release of some membrane-bound enzymes, such as AChE [43] or amyloid precursor protein (APP), which are crucial for the pathologic changes in the brains of AD patients. AlFx might affect the structure and function of cytoskeletal proteins by several routes [68]. It can activate various G-proteins and protein kinases, act as the analogue of GTP in the assembly-disassembly cycle, and affect the binding of cytoskeletal proteins to... 

The majority of this matrix is composed of a protein called spectrin, a heterodimeric protein containing a 220-kDa a subunit and a similar but slightly larger /3 subunit. The highly repetitive amino acid sequences of both the a and /3 subunits give them a filamentous three-dimensional structure. As the a and /3 subunits of spectrin associate with one another, they form the flexible monomeric units that are used to create the membrane skeleton. 

Tvo additional peripheral membrane proteins anchor the spectrin filaments to the cytoplasmic side of the erythrocyte membrane. One of these polypeptides, the 210-kDa ankyrin protein, binds both a single spectrin molecule and the chloride-bicarbonate anion-exchange protein discussed previously. The second of these polypeptides, actin, is capable of binding several molecules of spectrin. Since actin is able to associate with more than a single spectrin monomer, it acts as a branch point for the spectrin protein as the membrane skeleton or matrix is assembled (see Fig. 13-1). In this experiment, you will determine the concentration of total protein in the erythrocyte membrane through the use of the Folin-Ciocalteau assay. 

---