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Gene Review

alpha-Spec  -  alpha Spectrin

Drosophila melanogaster

Synonyms: 3A9, CG1977, Dmel\CG1977, FBtr0072789, FCP-B, ...
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Disease relevance of alpha-Spec


High impact information on alpha-Spec

  • Crumbs also regulates stalk development by stabilizing the membrane-associated spectrin cytoskeleton, a function mechanistically distinct from its role in epithelial apical-basal polarity [5].
  • Spectrin: a structural mediator between diverse plasma membrane proteins and the cytoplasm [6].
  • Organization of cells into tissues requires loss of cell motility, formation of specialized membrane domains and assembly of cell junctions, which are all activities potentially involving spectrin [6].
  • Examination of their erythrocyte membranes revealed abnormal mechanical stability as well as structural and functional abnormalities in spectrin [7].
  • The importance of leucine in this position of the proposed triple helical model of spectrin repeats is highlighted by its evolutionary conservation in all beta spectrins from Drosophila to humans [7].

Biological context of alpha-Spec

  • Here we used a genetic approach to directly test the requirement for the beta subunit of the alphabeta spectrin molecule in morphogenesis and function of epithelial cells in Drosophila. beta Spectrin mutations were lethal during late embryonic/early larval development and they produced subtle defects in midgut morphology and stomach acid secretion [8].
  • The persistence of ankyrin and beta-spectrin may explain the relatively mild phenotype of alpha-spectrin mutants during early Drosophila development [9].
  • Besides its structural role in red blood cells, the Spectrin network is thought to function in non-erythroid cells during protein targeting and membrane domain formation [10].
  • ADD-87 co-localises with F-actin and spectrin in the cortex of the oocyte through stage 10 of oogenesis, consistent with a possible role in cytoskeletal assembly or function predicted by mammalian studies [11].
  • Diversity among spectrin isoforms, especially their beta subunits, is associated with diversity in cell shape and membrane architecture [12].

Anatomical context of alpha-Spec

  • Spectrin has been proposed to function as a sorting machine that concentrates interacting proteins such as the Na,K ATPase within specialized plasma membrane domains of polarized cells [8].
  • A postsynaptic Spectrin scaffold defines active zone size, spacing, and efficacy at the Drosophila neuromuscular junction [13].
  • We suggest that Lva and Spectrin may form a Golgi-based scaffold that mediates the interaction of Golgi bodies with microtubules and facilitates Golgi-derived membrane secretion required for the formation of furrows during cellularization [14].
  • Germ line transformants carrying an alpha-spectrin cDNA, whose expression is driven by the ubiquitin promoter, fully rescued the first to second instar lethality characteristic of the l(3)dre3 alleles [15].
  • alpha-Spectrin is required for ovarian follicle monolayer integrity in Drosophila melanogaster [1].

Associations of alpha-Spec with chemical compounds

  • We find that the plakin repeats are inserted between the actin-binding domain and spectrin repeats, generating isoforms as large as 8,846 residues, which could span 400 nm [16].
  • The fusion proteins elicited antibodies that reacted strongly with Drosophila and vertebrate alpha-spectrins and a comparison of cyanogen bromide peptide maps demonstrated a clear structural correspondence between one fusion protein and purified Drosophila alpha-spectrin [17].
  • The subsequent three helices (helices A1, B1, and C1) form a triple helical bundle structural domain that is similar, but not identical, to previously published structures for spectrin from Drosophila and chicken brain [18].
  • The importance of isoleucine in this position of the proposed triple helical model of spectrin repeats is highlighted by its evolutionary conservation in all alpha spectrins from Drosophila to humans [19].
  • Molecular modeling demonstrated that replacement of a hydrophobic isoleucine with a hydrophilic threonine disrupts highly conserved hydrophobic interactions in the interior of the spectrin triple helix critical for spectrin function [19].

Physical interactions of alpha-Spec

  • First, a site responsible for calmodulin binding to Drosophila alpha spectrin was identified near the junction of repetitive segments 14 and 15 [20].

Other interactions of alpha-Spec

  • The results establish a role for beta spectrin in determining the subcellular distribution of the Na, K ATPase and, unexpectedly, this role is independent of alpha spectrin [8].
  • Adducin is a cytoskeletal protein that can function in vitro to bundle F-actin and to control the assembly of the F-actin/spectrin cytoskeletal network [11].
  • This region is closely related to the N-terminal segment of several src-tyrosine kinases and to a domain of phospholipase C. Like the spectrin alpha-chain, the major central part of the spectrin beta-chain is made up of repeat units of 106 amino-acids [21].
  • In Drosophila, the genomic organization of dlt is unusual. dlt shares its first untranslated exon with alpha-spectrin, and both genes are coexpressed throughout development [22].
  • Surprisingly, elimination of alpha-spectrin from follicle cells does not appear to prevent the assembly of conventional beta-spectrin and ankyrin at the lateral domain of the follicle cell plasma membrane [1].

Analytical, diagnostic and therapeutic context of alpha-Spec


  1. alpha-Spectrin is required for ovarian follicle monolayer integrity in Drosophila melanogaster. Lee, J.K., Brandin, E., Branton, D., Goldstein, L.S. Development (1997) [Pubmed]
  2. Crystal structure of the repetitive segments of spectrin. Yan, Y., Winograd, E., Viel, A., Cronin, T., Harrison, S.C., Branton, D. Science (1993) [Pubmed]
  3. Studies of the erythrocyte spectrin tetramerization region. Park, S., Mehboob, S., Luo, B.H., Hurtuk, M., Johnson, M.E., Fung, L.W. Cell. Mol. Biol. Lett. (2001) [Pubmed]
  4. A spectrin-like protein present on membranes of Amoeba proteus as studied with monoclonal antibodies. Choi, E.Y., Jeon, K.W. Exp. Cell Res. (1989) [Pubmed]
  5. Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis. Pellikka, M., Tanentzapf, G., Pinto, M., Smith, C., McGlade, C.J., Ready, D.F., Tepass, U. Nature (2002) [Pubmed]
  6. Spectrin: a structural mediator between diverse plasma membrane proteins and the cytoplasm. Bennett, V. Curr. Opin. Cell Biol. (1990) [Pubmed]
  7. Mutation of a highly conserved residue of betaI spectrin associated with fatal and near-fatal neonatal hemolytic anemia. Gallagher, P.G., Petruzzi, M.J., Weed, S.A., Zhang, Z., Marchesi, S.L., Mohandas, N., Morrow, J.S., Forget, B.G. J. Clin. Invest. (1997) [Pubmed]
  8. Drosophila beta spectrin functions independently of alpha spectrin to polarize the Na,K ATPase in epithelial cells. Dubreuil, R.R., Wang, P., Dahl, S., Lee, J., Goldstein, L.S. J. Cell Biol. (2000) [Pubmed]
  9. Ankyrin and beta-spectrin accumulate independently of alpha-spectrin in Drosophila. Dubreuil, R.R., Yu, J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  10. {beta}-Spectrin functions independently of Ankyrin to regulate the establishment and maintenance of axon connections in the Drosophila embryonic CNS. Garbe, D.S., Das, A., Dubreuil, R.R., Bashaw, G.J. Development (2007) [Pubmed]
  11. Differential distributions of two adducin-like protein isoforms in the Drosophila ovary and early embryo. Zaccai, M., Lipshitz, H.D. Zygote (1996) [Pubmed]
  12. A beta-spectrin isoform from Drosophila (beta H) is similar in size to vertebrate dystrophin. Dubreuil, R.R., Byers, T.J., Stewart, C.T., Kiehart, D.P. J. Cell Biol. (1990) [Pubmed]
  13. A postsynaptic Spectrin scaffold defines active zone size, spacing, and efficacy at the Drosophila neuromuscular junction. Pielage, J., Fetter, R.D., Davis, G.W. J. Cell Biol. (2006) [Pubmed]
  14. Lava lamp, a novel peripheral golgi protein, is required for Drosophila melanogaster cellularization. Sisson, J.C., Field, C., Ventura, R., Royou, A., Sullivan, W. J. Cell Biol. (2000) [Pubmed]
  15. Cell shape and interaction defects in alpha-spectrin mutants of Drosophila melanogaster. Lee, J.K., Coyne, R.S., Dubreuil, R.R., Goldstein, L.S., Branton, D. J. Cell Biol. (1993) [Pubmed]
  16. Maintaining epithelial integrity: a function for gigantic spectraplakin isoforms in adherens junctions. Röper, K., Brown, N.H. J. Cell Biol. (2003) [Pubmed]
  17. Drosophila spectrin. II. Conserved features of the alpha-subunit are revealed by analysis of cDNA clones and fusion proteins. Byers, T.J., Dubreuil, R., Branton, D., Kiehart, D.P., Goldstein, L.S. J. Cell Biol. (1987) [Pubmed]
  18. Solution structural studies on human erythrocyte alpha-spectrin tetramerization site. Park, S., Caffrey, M.S., Johnson, M.E., Fung, L.W. J. Biol. Chem. (2003) [Pubmed]
  19. Mutation of a highly conserved isoleucine disrupts hydrophobic interactions in the alpha beta spectrin self-association binding site. Gallagher, P.G., Zhang, Z., Morrow, J.S., Forget, B.G. Lab. Invest. (2004) [Pubmed]
  20. Structure, calmodulin-binding, and calcium-binding properties of recombinant alpha spectrin polypeptides. Dubreuil, R.R., Brandin, E., Reisberg, J.H., Goldstein, L.S., Branton, D. J. Biol. Chem. (1991) [Pubmed]
  21. The spectrin super-family. Dhermy, D. Biol. Cell (1991) [Pubmed]
  22. The Drosophila cell survival gene discs lost encodes a cytoplasmic Codanin-1-like protein, not a homolog of tight junction PDZ protein Patj. Pielage, J., Stork, T., Bunse, I., Klämbt, C. Dev. Cell (2003) [Pubmed]
  23. Drosophila spectrin: the membrane skeleton during embryogenesis. Pesacreta, T.C., Byers, T.J., Dubreuil, R., Kiehart, D.P., Branton, D. J. Cell Biol. (1989) [Pubmed]
  24. Drosophila development requires spectrin network formation. Deng, H., Lee, J.K., Goldstein, L.S., Branton, D. J. Cell Biol. (1995) [Pubmed]
  25. Association of spectrin with a subcompartment of the endoplasmic reticulum in honeybee photoreceptor cells. Baumann, O. Cell Motil. Cytoskeleton (1998) [Pubmed]
  26. Vanaso is a candidate quantitative trait gene for Drosophila olfactory behavior. Fanara, J.J., Robinson, K.O., Rollmann, S.M., Anholt, R.R., Mackay, T.F. Genetics (2002) [Pubmed]
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