Drosophila ankyrin 2 is required for synaptic stability.
Synaptic connections are stabilized through transsynaptic adhesion complexes that are anchored in the underlying cytoskeleton. The Drosophila neuromuscular junction (NMJs) serves as a model system to unravel genes required for the structural remodeling of synapses. In a mutagenesis screen for regulators of synaptic stability, we recovered mutations in Drosophila ankyrin 2 (ank2) affecting two giant Ank2 isoforms that are specifically expressed in the nervous system and associate with the presynaptic membrane cytoskeleton. ank2 mutant larvae show severe deficits in the stability of NMJs, resulting in a reduction in overall terminal size, withdrawal of synaptic boutons, and disassembly of presynaptic active zones. In addition, lack of Ank2 leads to disintegration of the synaptic microtubule cytoskeleton. Microtubules and microtubule-associated proteins fail to extend into distant boutons. Interestingly, Ank2 functions downstream of spectrin in the anchorage of synaptic microtubules, providing the cytoskeletal scaffold that is essential for synaptic stability.
Koch
Iris
I
Max-Planck-Institute for Developmental Biology, Department III/Genetics, Spemannstrasse 35, 72076 Tübingen, Germany.
Schwarz
Heinz
H
Beuchle
Dirk
D
Goellner
Bernd
B
Langegger
Maria
M
Aberle
Hermann
H
D000818:Animals; D030801:Animals, Genetically Modified; D017487:Ankyrins / Q000235:genetics / Q000502:physiology*; D016827:CD8 Antigens / Q000378:metabolism; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007814:Larva; D018613:Microscopy, Confocal / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism; D009469:Neuromuscular Junction / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology / Q000648:ultrastructure; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020539:Sequence Analysis, Protein; D013569:Synapses / Q000502:physiology*; D050857:Synaptotagmins / Q000378:metabolism; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism
C498993:Ank2 protein, Drosophila; D017487:Ankyrins; D016827:CD8 Antigens; D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; D009414:Nerve Growth Factors; D020033:Protein Isoforms; D050496:Vesicular Glutamate Transport Proteins; C409635:futsch protein, Drosophila; D050857:Synaptotagmins; D049452:Green Fluorescent Proteins