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.  J. Biol. Chem. 290(2): 706--715.

FBrf0227259

Research paper

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-spec(R22S), a tetramerization site mutant homologous to the pathological α-spec(R28S) allele in humans, eliminates detectable binding to β-spectrin and reduces binding to βH-spectrin ∼1000-fold. Even though spectrins are essential proteins, α-spectrin(R22S) 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.

PMC4294495 (PMC) (EuropePMC)