Dynamin 3 is a component of the postsynapse, where it interacts with mGluR5 and Homer
Dynamin 3 is a component of the postsynapse, where it interacts with mGluR5 and Homer
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DOI：
10.1016/s0960-9822(03)00136-2
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发表时间：
2003-03-18
期刊：
影响因子：
9.2
通讯作者：
McNiven, MA
中科院分区：
文献类型：
--
作者：
Gray, NW;Fourgeaud, L;McNiven, MA
动力蛋白包括一个已知参与膜建模事件的机械酶大家族[1,2]。所有三种常规动力蛋白基因（Dyn1, Dyn2, Dyn3）都在哺乳动物大脑中表达，并且由于选择性剪接[3]而产生超过27种不同的动力蛋白。过去的研究表明Dyn1参与特殊的神经元功能，如快速突触囊泡循环[4]，而Dyn2可能介导传统的网格蛋白介导的表面受体[5]的摄取。目前，Dyn3在神经元或任何其他细胞类型中的分布、表达和功能都完全不清楚。在这里，我们证明Dyn1和Dyn3在突触中的定位是不同的。Dyn1集中在突触前腔室，而Dyn3定位于树突棘尖端。在突触后密度（PSD）中，我们发现Dyn3，而不是Dyn1，是由Homer和代谢性谷氨酸受体组成的生化分离复合体的一部分。最后，虽然显性阴性Dyn3似乎不抑制受体内吞噬，但成熟神经元中特异性Dyn3剪接变体的过度表达引起了树突棘的显著重塑。这些数据表明Dyn3是一种突触后动力蛋白，和它的结合伙伴Homer一样，在树突棘的形态发生和重塑中起着重要作用。
The dynamins comprise a large family of mechanoenzymes known to participate in membrane modeling events [1, 2]. All three conventional dynamin genes (Dyn1, Dyn2, Dyn3) are expressed in mammalian brain and produce more than 27 different dynamin proteins as a result of alternative splicing [3]. Past studies have suggested that Dyn1 participates in specialized neuronal functions such as rapid synaptic vesicle recycling [4], while Dyn2 may mediate the conventional clathrin-mediated uptake of surface receptors [5]. Currently, the distribution, expression, and function of Dyn3 in neurons, or in any other cell type, are completely undefined. Here, we demonstrate that Dyn1 and Dyn3 localize differentially in the synapse. Dyn1 concentrates within the presynaptic compartment, while Dyn3 localizes to dendritic spine tips. Within the postsynaptic density (PSD), we found Dyn3, but not Dyn1, to be part of a biochemically isolated complex comprised of Homer and metabotropic glutamate receptors. Finally, although dominant-negative Dyn3 did not seem to inhibit receptor endocytosis, overexpression of a specific Dyn3 spliced variant in mature neurons caused a marked remodeling of dendritic spines. These data suggest that Dyn3 is a postsynaptic dynamin and, like its binding partner Homer, plays a significant role in dendritic spine morphogenesis and remodeling.