The EHD protein Past1 controls postsynaptic membrane elaboration and synaptic function.
The EHD protein Past1 controls postsynaptic membrane elaboration and synaptic function.
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DOI：
10.1091/mbc.e15-02-0093
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发表时间：
2015-09-15
影响因子：
3.3
通讯作者：
Rodal AA
中科院分区：
文献类型：
--
作者：
Koles K;Messelaar EM;Feiger Z;Yu CJ;Frank CA;Rodal AA
果蝇神经肌肉接头突触后膜重塑和突触传递需要保守的C-末端EHD蛋白Past 1。Past 1活性定义了BAR结构域蛋白Syndapin和Amphiphysin的不同突触微结构域，表明了突触后膜网状结构的新机制。膜形成了精心设计的结构，这些结构高度适应其专门的细胞功能，但这些结构形成的机制仍然知之甚少。在这里，我们表明，保守的膜重塑C-末端Eps 15同源结构域（EHD）蛋白Past 1所需的突触下肌膜网（SSR）在果蝇幼虫神经肌肉接头（NMJ）的正常组装。past 1突变体表现出改变的NMJ形态、减少的突触传递、降低的谷氨酸受体水平和突触稳态的缺陷。膜重塑蛋白Amphiphysin和Syndapin与Past 1共定位在不同的SSR亚结构域中，并在Past 1突变体的SSR中崩溃为Amphiphysin依赖性膜结节。我们的研究结果表明，多个脂质结合蛋白的协调行动导致的SSR层的增加，并发现新的作用EHD蛋白在突触的阐述机制。
The conserved C-terminal EHD protein Past1 is required for postsynaptic membrane remodeling and synaptic transmission at the Drosophila neuromuscular junction. Past1 activity defines distinct synaptic microdomains of the BAR-domain proteins Syndapin and Amphiphysin, suggesting a new mechanism for elaboration of the postsynaptic membrane reticulum. Membranes form elaborate structures that are highly tailored to their specialized cellular functions, yet the mechanisms by which these structures are shaped remain poorly understood. Here, we show that the conserved membrane-remodeling C-terminal Eps15 Homology Domain (EHD) protein Past1 is required for the normal assembly of the subsynaptic muscle membrane reticulum (SSR) at the Drosophila melanogaster larval neuromuscular junction (NMJ). past1 mutants exhibit altered NMJ morphology, decreased synaptic transmission, reduced glutamate receptor levels, and a deficit in synaptic homeostasis. The membrane-remodeling proteins Amphiphysin and Syndapin colocalize with Past1 in distinct SSR subdomains and collapse into Amphiphysin-dependent membrane nodules in the SSR of past1 mutants. Our results suggest a mechanism by which the coordinated actions of multiple lipid-binding proteins lead to the elaboration of increasing layers of the SSR and uncover new roles for an EHD protein at synapses.