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Gene Review

beta-Spec  -  beta Spectrin

Drosophila melanogaster

Synonyms: B-spec, CG5870, Dmel\CG5870, SPEC8, Spec, ...
 
 
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Disease relevance of beta-Spec

 

High impact information on beta-Spec

 

Biological context of beta-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 [4].
  • Here, we demonstrate that Drosophila karussell mutations affect beta-spectrin and lead to distinct axonal patterning defects in the embryonic CNS. karussell mutants display a slit-sensitive axonal phenotype characterized by axonal looping in stage-13 embryos [5].
  • We used a transgene rescue strategy in Drosophila melanogaster to test contributions of four specific functional sites in beta spectrin to its assembly and function [3].
  • Elimination of beta(H) prevents the stable recruitment of alpha-spectrin to the apical domain, but does not result in a loss of apicobasal polarity, as would be predicted from current models describing the role of spectrin in the establishment of cell polarity [6].
  • The primary amino acid sequence of each spectrin subunit is dominated by tandemly repeated 106-residue motifs [7].
 

Anatomical context of beta-Spec

  • alpha- and beta-Spectrin are major components of a submembrane cytoskeletal network connecting actin filaments to integral plasma membrane proteins [8].
  • The C-terminal extremity of the erythroid beta-chain is also of great interest, since tissue-specific differential processing of 3'beta-spectrin gene pre-mRNA generates a beta spectrin-isoform with a unique C-terminus in human skeletal muscle [9].
  • 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 [10].
  • Spectrin functions upstream of ankyrin in a spectrin cytoskeleton assembly pathway [3].
  • However, all cells that lack PAR-1 accumulate spectrin and F-actin laterally, and show a strong increase in the density of microtubules [11].
 

Associations of beta-Spec with chemical compounds

 

Regulatory relationships of beta-Spec

  • It was previously shown that ankyrin and beta spectrin are recruited to sites of cell-cell contact in Drosophila S2 cells expressing the homophilic adhesion molecule neuroglian [14].
 

Other interactions of beta-Spec

 

Analytical, diagnostic and therapeutic context of beta-Spec

References

  1. Beta spectrin kissimmee: a spectrin variant associated with autosomal dominant hereditary spherocytosis and defective binding to protein 4.1. Becker, P.S., Tse, W.T., Lux, S.E., Forget, B.G. J. Clin. Invest. (1993) [Pubmed]
  2. 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]
  3. Spectrin functions upstream of ankyrin in a spectrin cytoskeleton assembly pathway. Das, A., Base, C., Dhulipala, S., Dubreuil, R.R. J. Cell Biol. (2006) [Pubmed]
  4. 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]
  5. Distinct functions of {alpha}-Spectrin and {beta}-Spectrin during axonal pathfinding. Hülsmeier, J., Pielage, J., Rickert, C., Technau, G.M., Klämbt, C., Stork, T. Development (2007) [Pubmed]
  6. Apical spectrin is essential for epithelial morphogenesis but not apicobasal polarity in Drosophila. Zarnescu, D.C., Thomas, G.H. J. Cell Biol. (1999) [Pubmed]
  7. The complete sequence of Drosophila beta-spectrin reveals supra-motifs comprising eight 106-residue segments. Byers, T.J., Brandin, E., Lue, R.A., Winograd, E., Branton, D. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  8. {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]
  9. The spectrin super-family. Dhermy, D. Biol. Cell (1991) [Pubmed]
  10. 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]
  11. The role of PAR-1 in regulating the polarised microtubule cytoskeleton in the Drosophila follicular epithelium. Doerflinger, H., Benton, R., Shulman, J.M., St Johnston, D. Development (2003) [Pubmed]
  12. 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]
  13. 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]
  14. Segregation of two spectrin isoforms: polarized membrane-binding sites direct polarized membrane skeleton assembly. Dubreuil, R.R., Maddux, P.B., Grushko, T.A., MacVicar, G.R. Mol. Biol. Cell (1997) [Pubmed]
  15. 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]
  16. Drosophila development requires spectrin network formation. Deng, H., Lee, J.K., Goldstein, L.S., Branton, D. J. Cell Biol. (1995) [Pubmed]
 
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