Sanda Masashi, Kamata Akifumi, Katsumata Osamu, Fukunaga Kohji, Watanabe Masahiko, Kondo Hisatake, Sakagami Hiroyuki
Department of Anatomy, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
Brain Res. 2009 Jan 28;1251:7-15. doi: 10.1016/j.brainres.2008.11.061. Epub 2008 Dec 3.
IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor for Arf1 and Arf6, is localized at the postsynaptic density (PSD) and interacts with PSD-95. In this study, we identified a novel interaction of IQ-ArfGEF/BRAG1 with insulin receptor tyrosine kinase substrate of 53 kDa (IRSp53), also known as brain-specific angiogenesis inhibitor 1-associated protein 2. The interaction was mediated by the binding of the C-terminal proline-rich sequence of IQ-ArfGEF/BRAG1 to the SH3 domain of IRSp53. IQ-ArfGEF/BRAG1 and IRSp53 were colocalized at the PSD of excitatory synapses of certain neuronal populations. Our present findings suggest that IQ-ArfGEF/BRAG1 may play roles downstream of NMDA receptors through the interaction with multivalent PSD proteins such as IRSp53 and PSD-95.
IQ-ArfGEF/BRAG1是一种针对Arf1和Arf6的鸟嘌呤核苷酸交换因子，定位于突触后致密区（PSD）并与PSD-95相互作用。在本研究中，我们鉴定出IQ-ArfGEF/BRAG1与53 kDa胰岛素受体酪氨酸激酶底物（IRSp53，也称为脑特异性血管生成抑制因子1相关蛋白2）之间存在新型相互作用。这种相互作用是由IQ-ArfGEF/BRAG1富含脯氨酸的C末端序列与IRSp53的SH3结构域结合介导的。IQ-ArfGEF/BRAG1和IRSp53在某些神经元群体兴奋性突触的PSD处共定位。我们目前的研究结果表明，IQ-ArfGEF/BRAG1可能通过与诸如IRSp53和PSD-95等多价PSD蛋白相互作用，在NMDA受体下游发挥作用。
