Evolutionary insights into premetazoan functions of the neuronal protein homer.

Evolutionary insights into premetazoan functions of the neuronal protein homer.
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DOI:
10.1093/molbev/msu178
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发表时间:
2014-09
影响因子:
10.7
通讯作者:
King N
King N
中科院分区:
生物学1区
文献类型:
--
作者:
Burkhardt P;Grønborg M;McDonald K;Sulur T;Wang Q;King N

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重建突触蛋白的进化和祖先功能有望揭示神经元最初是如何进化的。突触后密度(PSD)蛋白Homer在多种后生动物细胞类型(包括神经元和肌肉细胞)中支撑膜受体并调节Ca2+信号,但其起源和核心功能尚不清楚。我们发现,后生动物荷马蛋白的蛋白质结构域组织和基本生化特性,包括它们的四聚体能力,在后生动物最近的近亲之一——尾鞭毛虫(Salpingoeca rosetta)中是保守的。与神经元不同,Homer定位于s.s rosetta的核质,并直接与Flotillin(一种通常与细胞膜相关的蛋白质)相互作用。令人惊讶的是,我们发现Homer/Flotillin相互作用及其在细胞核中的定位在后动物星形胶质细胞中是保守的。这些发现表明,Homer最初在后生动物和鞭毛动物的最后共同祖先的细胞核中与Flotillin相互作用,后来在PSD中作为膜受体支架发挥作用。
Reconstructing the evolution and ancestral functions of synaptic proteins promises to shed light on how neurons first evolved. The postsynaptic density (PSD) protein Homer scaffolds membrane receptors and regulates Ca2+ signaling in diverse metazoan cell types (including neurons and muscle cells), yet its ancestry and core functions are poorly understood. We find that the protein domain organization and essential biochemical properties of metazoan Homer proteins, including their ability to tetramerize, are conserved in the choanoflagellate Salpingoeca rosetta, one of the closest living relatives of metazoans. Unlike in neurons, Homer localizes to the nucleoplasm in S. rosetta and interacts directly with Flotillin, a protein more commonly associated with cell membranes. Surprisingly, we found that the Homer/Flotillin interaction and its localization to the nucleus are conserved in metazoan astrocytes. These findings suggest that Homer originally interacted with Flotillin in the nucleus of the last common ancestor of metazoans and choanoflagellates and was later co-opted to function as a membrane receptor scaffold in the PSD.
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