Spectrin tetramer formation is not required for viable development in drosophila

Mansi R. Khanna, Floyd J. Mattie, Kristen C. Browder, Megan D. Radyk, Stephanie E. Crilly, Katelyn J. Bakerink, Sandra L. Harper, David W. Speicher, Graham H. Thomas

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The dominant paradigm for spectrin function is that (β)2-spectrin tetramers or higher order oligomers form membrane associated two-dimensional networks in association with F-actin to reinforce the plasma membrane. Tetramerization is an essential event in such structures.Wecharacterize the tetramerization interaction between α-spectrin and β-spectrins in Drosophila. Wild-type α-spectrin binds to both β- and βH-chains with high affinity, resembling other non-erythroid spectrins. However, α- specR22S, a tetramerization site mutant homologous to the pathological -αr28s allele in humans, eliminates detectable binding toα-spectrin and reduces binding to βH-spectrin ∼1000-fold. Even though spectrins are essential proteins, α-spectrinR22S rescuesα-spectrin mutants to adulthood with only minor phenotypes indicating that tetramerization, and thus conventional network formation, is not the essential function of non-erythroid spectrin. Our data provide the first rigorous test for the general requirement for tetramerbased non-erythroid spectrin networks throughout an organism and find that they have very limited roles, in direct contrast to the current paradigm.

Original languageEnglish (US)
Pages (from-to)706-715
Number of pages10
JournalJournal of Biological Chemistry
Volume290
Issue number2
DOIs
StatePublished - Jan 9 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Khanna, M. R., Mattie, F. J., Browder, K. C., Radyk, M. D., Crilly, S. E., Bakerink, K. J., Harper, S. L., Speicher, D. W., & Thomas, G. H. (2015). Spectrin tetramer formation is not required for viable development in drosophila. Journal of Biological Chemistry, 290(2), 706-715. https://doi.org/10.1074/jbc.M114.615427