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.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology