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Abstract:
Once synapses have formed, functionally importantconnections have to be maintained and stabilized, mostlyby transsynaptic adhesion complexes that are anchored inthe underlying cytoskeleton. The Drosophila neuromus-cular junction (NMJ) serves as a model system for centralsynapses in the vertebrate brain, as both synapse typesshare molecular and structural features. In a mutagenesisscreen for regulators of synaptic stability, we recoveredmutations in Drosophila ankyrin 2 (ank2) affecting twogiant Ank2 isoforms that are specifically expressed in thenervous system, and that are tightly associated with thepresynaptic membrane cytoskeleton. ank2 mutant larvaeshow severe deficits in the stability of NMJs, resulting ina reduction in overall terminal size. Synaptic boutons arewithdrawn and presynaptic active zones are disassembled.In addition, lack of Ank2 leads to disintegration of thesynaptic microtubule cytoskeleton. Microtubules andmicrotubule-associated proteins fail to extend into distantboutons. Interestingly, Ank2 functions downstream ofSpectrin in the anchorage of synaptic microtubules,providing a cytoskeletal scaffold that is essential forsynaptic stability
