The erythrocyte membrane skeleton is the best understood cytoskeleton. Because its protein components have homologs in virtually all other cells, the membrane serves as a fundamental model of biologic membranes. Modern textbooks portray the membrane as a 2-dimensional spectrin-based membrane skeleton attached to a lipid bilayer through 2 linkages: band 3-ankyrin-␤-spectrin and glycophorin C-protein 4.1-␤-spectrin. 1-7 Although evidence supports an essential role for the first bridge in regulating membrane cohesion, rupture of the glycophorin C-protein 4.1 interaction has little effect on membrane stability. 8 We demonstrate the existence of a novel band 3-adducin-spectrin bridge that connects the spectrin/actin/protein 4.1 junctional complex to the bilayer. As rupture of this bridge leads to spontaneous membrane fragmentation, we conclude that the band 3-adducinspectrin bridge is important to membrane stability. The required relocation of part of the band 3 population to the spectrin/actin junctional complex and its formation of a new bridge with adducin necessitates a significant revision of accepted models of the erythrocyte membrane. (Blood. 2009;114: 1904-1912 IntroductionThe model of the erythrocyte membrane presented in cell biology, hematology, and biochemistry textbooks shows 2 major protein bridges that span between the phospholipid bilayer and the spectrin/actin skeleton. [1][2][3][4][5][6][7] The more prominent bridge, a linkage from the integral membrane protein, band 3, to spectrin via ankyrin, is composed of multiple high-affinity protein-protein interactions. [9][10][11] Defects or deficiencies in either band 3 or ankyrin lead to a decrease in cohesion between the lipid bilayer and membrane skeleton, resulting in loss of membrane surface area and a pathology termed hereditary spherocytosis. [12][13][14] Manual rupture of this bridge by addition of competing fragments of either band 3 or ankyrin, or by addition of competing monoclonal antibodies, or mutation of the ankyrin binding site on band 3 induces spontaneous membrane vesiculation and fragmentation. [14][15][16] Spontaneous mutations in the ankyrin-bridging function in other cells can also lead to serious pathologies. [17][18][19][20] Taken together, these data support the importance of the ankyrin-spectrin bridge in maintaining membrane integrity.The second bridge connecting the membrane bilayer to the spectrinactin skeleton consists of the membrane-spanning protein, glycophorin C (GPC), tethered to spectrin via the adapter protein 4.1. [21][22][23] The complex of cytoskeletal proteins at this nexus (primarily actin, dematin, tropomyosin, adducin, protein 4.1, and tropomodulin) forms a junctional complex from which spectrin tetramers extend radially into a 2-dimensional lattice that provides mechanical stability to the overlying membrane. Based on the finding that GPC-deficient red cells exhibit decreased membrane mechanical stability, it has been inferred that the GPC-protein 4.1 bridge is essential to erythrocyte integrity. 24,25 However...

Adducin is an α, β heterotetramer that performs multiple important functions in the human erythrocyte membrane. First, adducin forms a bridge that connects the spectrin–actin junctional complex to band 3, the major membrane-spanning protein in the bilayer. Rupture of this bridge leads to membrane instability and spontaneous fragmentation. Second, adducin caps the fast growing (barbed) end of actin filaments, preventing the tetradecameric protofilaments from elongating into macroscopic F-actin microfilaments. Third, adducin stabilizes the association between actin and spectrin, assuring that the junctional complex remains intact during the mechanical distortions experienced by the circulating cell. And finally, adducin responds to stimuli that may be important in regulating the global properties of the cell, possibly including cation transport, cell morphology and membrane deformability. The text below summarizes the structural properties of adducin, its multiple functions in erythrocytes, and the consequences of engineered deletions of each of adducin subunits in transgenic mice.

The synthesis of non-linear optical (NLO) materials that are transparent into the deep-UV (<200 nm) region is an important component in the development of advanced optical technology. Such materials are sought after for their potential applications in the fields of high resolution photolithography, micro-machining, and laser spectroscopy. Borates are one class of solid-state materials that have received consideration for these applications because of their favorable physical and optical properties. One such compound, Sr2Be2B2O7 (SBBO) has been reported to be transparent below 200 nm, and exhibits a large second harmonic generation (SHG) coefficient. Significant difficulties in the flux growth of large, high quality crystals have prevented this material from further development. We have successfully grown large crystals of SBBO by a hydrothermal synthetic method for the first time, and have characterized their physical properties. The synthesis and structure of a new material encountered during the synthesis of SBBO, LiBeSr2B3O8, is also reported here.

Two major complexes form structural bridges that connect the erythrocyte membrane to its underlying spectrin-based cytoskeleton. Although the band 3-ankyrin bridge may account for most of the membrane-to-cytoskeleton interactions, the linkage between the cytoplasmic domain of band 3 (cdb3) and adducin has also been shown to be critical to membrane integrity. In this paper, we demonstrate that adducin, a major component of the spectrin-actin junctional complex, binds primarily to residues 246 through 264 of cdb3, and mutation of two exposed glutamic acid residues within this sequence completely abrogates both α- and β-adducin binding. Because these residues are located next to the ankyrin binding site on cdb3, it seems unlikely that band 3 can bind ankyrin and adducin concurrently, reducing the chances of an association between the ankyrin and junctional complexes that would significantly compromise erythrocyte membrane integrity. We also demonstrate the adducin binds the kidney isoform of cdb3, a spliceoform that lacks the first 65 amino acids of erythrocyte cdb3, including the central strand of a large beta-pleated sheet. Because kidney cdb3 is not known to bind any of the common peripheral protein partners of erythrocyte cdb3, including ankyrin, protein 4.1, glyceraldehyde-3-phosphate dehydrogenase, aldolase, and phosphofructokinase, retention of this affinity for adducin was unexpected.