Hts/Adducin Controls Synaptic Elaboration and Elimination
被引:84
作者:
Pielage, Jan
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Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA
Friedrich Miescher Inst Biomed Res, CH-4058 Basel, SwitzerlandUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA
Pielage, Jan
[1
,3
]
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Bulat, Victoria
[3
]
Zuchero, J. Bradley
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机构:
Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USAUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA
Zuchero, J. Bradley
[2
]
Fetter, Richard D.
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Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USAUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA
Fetter, Richard D.
[1
]
Davis, Graeme W.
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Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USAUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA
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
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.
机构:
Univ Calif San Francisco, Sch Med, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USAUniv Calif San Francisco, Sch Med, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA
Akin, Orkun
;
Mullins, R. Dyche
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Univ Calif San Francisco, Sch Med, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USAUniv Calif San Francisco, Sch Med, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA
机构:
Univ Calif San Francisco, Sch Med, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USAUniv Calif San Francisco, Sch Med, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA
Akin, Orkun
;
Mullins, R. Dyche
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h-index: 0
机构:
Univ Calif San Francisco, Sch Med, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USAUniv Calif San Francisco, Sch Med, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA