Proper synaptic vesicle formation and neuronal network activity critically rely on syndapin I
Proper synaptic vesicle formation and neuronal network activity critically rely on syndapin I
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DOI：
10.1038/emboj.2011.339
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发表时间：
2011-12-14
期刊：
影响因子：
11.4
通讯作者：
Qualmann, Britta
中科院分区：
文献类型：
--
作者：
Koch, Dennis;Spiwoks-Becker, Isabella;Qualmann, Britta
突触传递依赖于有效且准确的补偿性内吞作用。 F-BAR 蛋白可充当膜曲率传感器和/或诱导剂，从而支持膜重塑过程；然而，它们的体内功能亟待揭示。我们证明 F-BAR 蛋白 syndapin I 对于正常的大脑功能至关重要。 Syndapin I 敲除 (KO) 小鼠会出现癫痫发作，这种表型与海马网络过度活动一致。 Syndapin I 的缺失会导致突触前膜运输过程的缺陷，这在高容量检索条件下尤其明显，内吞中间体的积累，突触小泡 (SV) 大小控制的丧失，活动依赖性 SV 检索受损和突触活动缺陷。详细的分子分析表明，syndapin I 在将所有动力异构体（囊泡裂变反应的核心参与者）募集到膜上方面发挥着重要作用。一致地，syndapin I KO 小鼠与 dynamin I KO 小鼠具有相同的表型，而它们的癫痫表型很容易让人想起表达突变动力的断断续续的小鼠。因此，syndapin I 在 SV 再生过程中充当动力蛋白的关键膜锚定因子。 EMBO 杂志 (2011) 30, 4955-4969。 doi：10.1038/emboj.2011.339； 2011 年 9 月 16 日在线发布
Synaptic transmission relies on effective and accurate compensatory endocytosis. F-BAR proteins may serve as membrane curvature sensors and/or inducers and thereby support membrane remodelling processes; yet, their in vivo functions urgently await disclosure. We demonstrate that the F-BAR protein syndapin I is crucial for proper brain function. Syndapin I knockout (KO) mice suffer from seizures, a phenotype consistent with excessive hippocampal network activity. Loss of syndapin I causes defects in presynaptic membrane trafficking processes, which are especially evident under high-capacity retrieval conditions, accumulation of endocytic intermediates, loss of synaptic vesicle (SV) size control, impaired activity-dependent SV retrieval and defective synaptic activity. Detailed molecular analyses demonstrate that syndapin I plays an important role in the recruitment of all dynamin isoforms, central players in vesicle fission reactions, to the membrane. Consistently, syndapin I KO mice share phenotypes with dynamin I KO mice, whereas their seizure phenotype is very reminiscent of fitful mice expressing a mutant dynamin. Thus, syndapin I acts as pivotal membrane anchoring factor for dynamins during regeneration of SVs. The EMBO Journal (2011) 30, 4955-4969. doi: 10.1038/emboj.2011.339; Published online 16 September 2011