Hirao K, Hata Y, Yao I, Deguchi M, Kawabe H, Mizoguchi A, Takai Y
Takai Biotimer Project, ERATO, Japan Science and Technology Corporation, JCR Pharmaceuticals Company Limited, 2-2-10 Murotani, Nishi-ku, Kobe 651-2241, Japan.
J Biol Chem. 2000 Jan 28;275(4):2966-72. doi: 10.1074/jbc.275.4.2966.
The synaptic scaffolding molecule (S-SCAM) has been identified as a protein interacting with SAP90/PSD-95-associated protein (SAPAP) (also called guanylate kinase-associated protein/hDLG-associated protein). S-SCAM has six PDZ (we have numbered them PDZ-0 to -5), two WW, and one guanylate kinase (GK) domains and interacts with N-methyl-D-aspartate (NMDA) receptor via PDZ-5 and SAPAP via the GK domain. We have identified here shorter isoforms of S-SCAM that start at the 164th or 224th methionine, and we renamed the original one, S-SCAMalpha, the middle one, S-SCAMbeta, and the shortest one, S-SCAM-gamma. S-SCAMbeta and -gamma have five PDZ (PDZ-1 to -5), two WW, and one GK domains. S-SCAMalpha interacted with S-SCAMbeta and -gamma through the region containing PDZ-4 and -5. The region containing both of PDZ-4 and -5 is sufficient for the clustering of NMDA receptors and forms a dimer in gel filtration, suggesting that S-SCAM forms multimers via the interaction between the C-terminal PDZ domains and assembles NMDA receptors into clusters. S-SCAMbeta and -gamma also interacted with SAPAP, suggesting that the N-terminal region of the GK domain is not necessary for the interaction. Finally, we have identified the interaction of the PDZ domains of S-SCAM with the GK domain of PSD-95/SAP90. S-SCAM, PSD-95/SAP90, and SAPAP are colocalized at least in some part in brain. Therefore, S-SCAM, PSD-95/SAP90, and SAPAP may form a complex in vivo.
突触支架分子（S-SCAM）已被鉴定为一种与SAP90/PSD-95相关蛋白（SAPAP，也称为鸟苷酸激酶相关蛋白/hDLG相关蛋白）相互作用的蛋白质。S-SCAM具有六个PDZ结构域（我们将其编号为PDZ-0至-5）、两个WW结构域和一个鸟苷酸激酶（GK）结构域，并通过PDZ-5与N-甲基-D-天冬氨酸（NMDA）受体相互作用，通过GK结构域与SAPAP相互作用。我们在此鉴定出了S-SCAM的较短异构体，它们起始于第164位或第224位甲硫氨酸，我们将原始的异构体重新命名为S-SCAMα，中间的异构体命名为S-SCAMβ，最短的异构体命名为S-SCAMγ。S-SCAMβ和γ具有五个PDZ结构域（PDZ-1至-5）、两个WW结构域和一个GK结构域。S-SCAMα通过包含PDZ-4和-5的区域与S-SCAMβ和γ相互作用。同时包含PDZ-4和-5的区域足以使NMDA受体聚集，并且在凝胶过滤中形成二聚体，这表明S-SCAM通过C末端PDZ结构域之间的相互作用形成多聚体，并将NMDA受体组装成簇。S-SCAMβ和γ也与SAPAP相互作用，这表明GK结构域的N末端区域对于这种相互作用并非必需。最后，我们鉴定出了S-SCAM的PDZ结构域与PSD-95/SAP90的GK结构域之间的相互作用。S-SCAM、PSD-95/SAP90和SAPAP至少在大脑的某些部分共定位。因此，S-SCAM、PSD-95/SAP90和SAPAP可能在体内形成复合物。
