Spectrin tetramer formation is not required for viable development in Drosophila.

ABSTRACT: The dominant paradigm for spectrin function is that (??)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 ?-spectrin and ?-spectrins in Drosophila. Wild-type ?-spectrin binds to both ?- and ?H-chains with high affinity, resembling other non-erythroid spectrins. However, ?-spec(R22S), a tetramerization site mutant homologous to the pathological ?-spec(R28S) allele in humans, eliminates detectable binding to ?-spectrin and reduces binding to ?H-spectrin ?1000-fold. Even though spectrins are essential proteins, ?-spectrin(R22S) rescues ?-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.

SUBMITTER: Khanna MR 

PROVIDER: S-EPMC4294495 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature