Hts/Adducin Controls Synaptic Elaboration and Elimination

被引:84
作者
Pielage, Jan [1 ,3 ]
Bulat, Victoria [3 ]
Zuchero, J. Bradley [2 ]
Fetter, Richard D. [1 ]
Davis, Graeme W. [1 ]
机构
[1] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA
[2] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA
[3] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland
关键词
DROSOPHILA NEUROMUSCULAR-JUNCTION; FILAMENT NUCLEATION; ACTIN-FILAMENTS; ALPHA-ADDUCIN; CELL MOTILITY; BETA-ADDUCIN; IN-VIVO; F-ACTIN; PROTEIN; PLASTICITY;
D O I
10.1016/j.neuron.2011.02.007
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
Neural development requires both synapse elaboration and elimination, yet relatively little is known about how these opposing activities are coordinated. Here, we provide evidence Hts/Adducin can serve this function. We show that Drosophila Hts/Adducin is enriched both pre- and postsynaptically at the NMJ. We then demonstrate that presynaptic Hts/Adducin is necessary and sufficient to control two opposing processes associated with synapse remodeling: (1) synapse stabilization as determined by light level and ultrastructural and electrophysiological assays and (2) the elaboration of actin-based, filopodia-like protrusions that drive synaptogenesis and growth. Synapse remodeling is sensitive to Hts/Adducin levels, and we provide evidence that the synaptic localization of Hts/Adducin is controlled via phosphorylation. Mechanistically, Drosophila Hts/Adducin protein has actin-capping activity. We propose that phosphorylation-dependent regulation of Hts/Adducin controls the level, localization, and activity of Hts/Adducin, influencing actin-based synapse elaboration and spectrin-based synapse stabilization. Hts/Adducin may define a mechanism to switch between synapse stability and dynamics.
引用
收藏
页码:1114 / 1131
页数:18
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