Interaction of Cupidin/Homer2 with two actin cytoskeletal regulators, Cdc42 small GTPase and Drebrin, in dendritic spines.
Interaction of Cupidin/Homer2 with two actin cytoskeletal regulators, Cdc42 small GTPase and Drebrin, in dendritic spines.
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DOI：
10.1186/1471-2202-10-25
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发表时间：
2009-03-24
期刊：
影响因子：
2.4
通讯作者：
Furuichi T
中科院分区：
文献类型：
--
作者：
Shiraishi-Yamaguchi Y;Sato Y;Sakai R;Mizutani A;Knöpfel T;Mori N;Mikoshiba K;Furuichi T
Homer是一种突触后支架蛋白，连接各种突触信号蛋白，包括I型代谢型谷氨酸受体亚基1α和5、肌醇1，4，5-三磷酸受体、Shank和Cdc 42小GT3。Homer的过表达诱导培养的海马神经元树突棘形态的变化。然而，支持Homer介导的棘形态发生的分子基础仍然不清楚。在这项研究中，我们的目的是阐明Cupidin/Homer 2和两个肌动蛋白细胞骨架调节剂，Cdc 42小GTdR和DredR之间的相互作用的结构和功能特性。Cupidin/Homer 2通过位于C-末端卷曲螺旋结构域内的氨基酸残基191-283周围的Cdc 42结合结构域与活化的Cdc 42小GT α相互作用。我们构建了缺失191-230位氨基酸的Cupidin缺失突变体（CPDΔ191-230），其表现出降低的Cdc 42结合能力，但保持了自身多聚化能力。Cupidin抑制Cdc 42诱导的HeLa细胞丝状伪足样突起的形成，而CPDΔ191-230则不能。在培养的海马神经元中，Cupidin靶向于树突棘，而CPDΔ191-230分布于树突轴以及棘。CPDΔ191-230的过表达减少了海马神经元突触的数目，降低了兴奋性突触后电流的幅度。Cupidin通过N-末端EVH-1结构域与具有两个Homer配体基序的树突棘F-肌动蛋白结合蛋白Dreplatin相互作用。CPDΔ191-230过表达可减少海马神经元树突棘中的Drexine聚集。这些结果表明，Cupidin/Homer 2相互作用的树突棘肌动蛋白调节Cdc 42和Dredlymphocytes通过其C-末端和N-末端结构域，分别，它可能参与棘形态和突触特性。
Homer is a postsynaptic scaffold protein that links various synaptic signaling proteins, including the type I metabotropic glutamate receptor subunits 1α and 5, the inositol 1,4,5-trisphosphate receptor, Shank and Cdc42 small GTPase. Overexpression of Homer induces changes in dendritic spine morphology in cultured hippocampal neurons. However, the molecular basis underpinning Homer-mediated spine morphogenesis remains unclear. In this study, we aimed to elucidate the structural and functional properties of the interaction between Cupidin/Homer2 and two actin-cytoskeletal regulators, Cdc42 small GTPase and Drebrin. Cupidin/Homer2 interacted with activated Cdc42 small GTPase via the Cdc42-binding domain that resides around amino acid residues 191–283, within the C-terminal coiled-coil domain. We generated a Cupidin deletion mutant lacking amino acids 191–230 (CPDΔ191–230), which showed decrease Cdc42-binding ability but maintained self-multimerization ability. Cupidin suppressed Cdc42-induced filopodia-like protrusion formation in HeLa cells, whereas CPDΔ191–230 failed to do so. In cultured hippocampal neurons, Cupidin was targeted to dendritic spines, whereas CPDΔ191–230 was distributed in dendritic shafts as well as spines. Overexpression of CPDΔ191–230 decreased the number of synapses and reduced the amplitudes of miniature excitatory postsynaptic currents in hippocampal neurons. Cupidin interacted with a dendritic spine F-actin-binding protein, Drebrin, which possesses two Homer ligand motifs, via the N-terminal EVH-1 domain. CPDΔ191–230 overexpression decreased Drebrin clustering in the dendritic spines of hippocampal neurons. These results indicate that Cupidin/Homer2 interacts with the dendritic spine actin regulators Cdc42 and Drebrin via its C-terminal and N-terminal domains, respectively, and that it may be involved in spine morphology and synaptic properties.
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影响因子：
4.8
作者：
Kreis, Patricia;Thévenot, Emmanuel;Barnier, Jean-Vianney
通讯作者：
Barnier, Jean-Vianney
影响因子：
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影响因子：
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作者：
Shiraishi, Y;Mizutani, A;Furuichi, T
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Furuichi, T
影响因子：
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Shiraishi, Y;Mizutani, A;Furuichi, T
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