Ohtsuka T, Hata Y, Ide N, Yasuda T, Inoue E, Inoue T, Mizoguchi A, Takai Y
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, 565-0871, Japan.
Biochem Biophys Res Commun. 1999 Nov;265(1):38-44. doi: 10.1006/bbrc.1999.1619.
Synaptic scaffolding molecule (S-SCAM) has six PDZ domains through which it interacts with N-methyl-d-aspartate receptors and neuroligin at synaptic junctions. We isolated here a novel S-SCAM-binding protein. This protein has one PDZ, one Ras association, one Ras GDP/GTP exchange protein (Ras GEP) domain, and one C-terminal consensus motif for binding to PDZ domains. We named it nRap GEP (neural Rap GEP). nRap GEP moreover has an incomplete cyclic AMP (cAMP)-binding (CAB) domain. The domain organization of nRap GEP is similar to that of Epac/cAMP-guanine nucleotide exchange factor (GEF) I, except that Epac/cAMP-GEFI has complete CAB and Ras GEP domains but lacks the other two domains and the C-terminal motif. nRap GEP showed GEP activity for Rap1 but did not bind cAMP. nRap GEP was specifically expressed in rat brain. Immunohistochemical analysis revealed that nRap GEP and S-SCAM were localized at synaptic areas of the cerebellum. These results suggest that nRap GEP is a novel neural Rap1-specific GEP which is associated with S-SCAM.
突触支架分子（S-SCAM）具有六个PDZ结构域，通过这些结构域它在突触连接处与N-甲基-D-天冬氨酸受体和神经连接蛋白相互作用。我们在此分离出一种新型的S-SCAM结合蛋白。该蛋白具有一个PDZ结构域、一个Ras结合结构域、一个Ras GDP/GTP交换蛋白（Ras GEP）结构域以及一个用于与PDZ结构域结合的C末端共有基序。我们将其命名为nRap GEP（神经Rap GEP）。此外，nRap GEP具有一个不完整的环磷酸腺苷（cAMP）结合（CAB）结构域。nRap GEP的结构域组织与Epac/cAMP-鸟嘌呤核苷酸交换因子（GEF）I相似，不同之处在于Epac/cAMP-GEFI具有完整的CAB和Ras GEP结构域，但缺少另外两个结构域和C末端基序。nRap GEP对Rap1显示出GEP活性，但不结合cAMP。nRap GEP在大鼠脑中特异性表达。免疫组织化学分析表明，nRap GEP和S-SCAM定位于小脑的突触区域。这些结果表明，nRap GEP是一种与S-SCAM相关的新型神经Rap1特异性GEP。
