The phospho-dependent dynamin-syndapin interaction triggers activity-dependent bulk endocytosis of synaptic vesicles.
The phospho-dependent dynamin-syndapin interaction triggers activity-dependent bulk endocytosis of synaptic vesicles.
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DOI：
10.1523/jneurosci.1976-09.2009
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发表时间：
2009-06-17
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影响因子：
--
通讯作者：
Cousin MA
中科院分区：
文献类型：
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作者：
Clayton EL;Anggono V;Smillie KJ;Chau N;Robinson PJ;Cousin MA
在中枢神经末梢，突触囊泡（SV）可通过多种方式回收。在轻度刺激期间，主要的SV回收途径是经典的网格蛋白介导的内吞作用（CME）。在升高的神经元活动的活动依赖性大量内吞作用（ADBE）占主导地位，这需要激活的钙依赖性蛋白磷酸酶钙调磷酸酶。我们现在报告说，钙调磷酸酶去磷酸化动力蛋白I在神经末梢仅高于相同的活动阈值，触发ADBE。当发动蛋白I上的两个主要磷酸化位点被扰动时，ADBE被逮捕，这表明发动蛋白I去磷酸化是其激活的关键步骤。发动蛋白I去磷酸化刺激特定的发动蛋白I-syndapin I相互作用。这种相互作用的抑制竞争性肽或定点诱变只抑制ADBE，但不影响CME。结果表明，磷酸依赖的动力蛋白syndapin相互作用招募ADBE大量增加SV的内吞作用的条件下，神经元活动的升高。
Synaptic vesicles (SVs) are retrieved by more than one mode in central nerve terminals. During mild stimulation the dominant SV retrieval pathway is classical clathrin-mediated endocytosis (CME). During elevated neuronal activity activity-dependent bulk endocytosis (ADBE) predominates, which requires activation of the calcium-dependent protein phosphatase calcineurin. We now report that calcineurin dephosphorylates dynamin I in nerve terminals only above the same activity threshold that triggers ADBE. ADBE was arrested when the two major phospho-sites on dynamin I were perturbed, suggesting dynamin I dephosphorylation is a key step in its activation. Dynamin I dephosphorylation stimulates a specific dynamin I-syndapin I interaction. Inhibition of this interaction by competitive peptides or by site-directed mutagenesis exclusively inhibited ADBE but did not affect CME. The results reveal that the phospho-dependent dynamin-syndapin interaction recruits ADBE to massively increase SV endocytosis under conditions of elevated neuronal activity.