Biochemical and cell biological characterization of dysbindin-1

我们试图阐明dysbinding -1（一种精神分裂症相关分子）在神经组织中的生理作用。通过免疫荧光分析，我们发现dysbinding -1定位于原代培养的大鼠海马神经元的树突棘。rnai介导的dysbinding -1敲低导致产生异常拉长的未成熟树突状突起。我们发现WAVE2是dysbinding -1的结合伙伴。我们还发现，参与脊柱发育的WAVE2的结合分子Abi-1与dysbinding -1相互作用。dysbinding -1、WAVE2和Abi-1形成三元配合物，dysbinding -1促进WAVE2/Abi-1形成配合物。这些结果表明dysbinding -1可能通过与WAVE2和Abi-1的相互作用调控树突棘的形态发生。

We attempted to clarify physiological roles of dysbindin-1, a schizophrenia-related molecule, in nervous tissues. From immunofluorescence analysis, we found that dysbindin-1 localized at dendritic spines in primary cultured rat hippocampal neurons. RNAi-mediated dysbindin-1 knockdown led to the generation of abnormally elongated immature dendritic protrusions. We identified WAVE2 as a binding partner for dysbindin-1. We also found that Abi-1, a binding molecule for WAVE2 involved in spine development, interacts with dysbindin-1. While dysbindin-1, WAVE2 and Abi-1 formed ternary complex, dysbindin-1 promoted the WAVE2/Abi-1 complex formation. These results indicate possible roles of dysbindin-1 in the regulation of dendritic spine morphogenesis through the interaction with WAVE2 and Abi-1.