Spectrin Tetramer Formation Is Not Required for Viable Development in Drosophila

The dominant paradigm for spectrin function is that (αβ)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. We characterize 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 α-specR28S allele in humans, eliminates detectable binding to β-spectrin and reduces binding to βH-spectrin ∼1000-fold. Even though spectrins are essential proteins, α-spectrinR22S rescues α-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 tetramer-based non-erythroid spectrin networks throughout an organism and find that they have very limited roles, in direct contrast to the current paradigm.Underneath the membrane of most animal cells is a network (membrane skeleton) assembled using tetramers of the protein spectrin. Although spectrins are essential proteins, tetramer formation is surprisingly unimportant for Drosophila development. The major roles of the membrane skeleton do not require a conventional network. The ubiquitous model of the spectrin-based membrane skeleton has limited applicability.