Synaptic scaffolding molecule interacts with Axin

Synaptic scaffolding molecule interacts with Axin
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DOI:
10.1111/j.1471-4159.2004.02497.x
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发表时间:
2004-07-01
影响因子:
4.7
通讯作者:
Hata, Y
Hata, Y
中科院分区:
医学2区
文献类型:
--
作者:
Hirabayashi, S;Nishimura, W;Hata, Y

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突触支架分子(Synaptic scaffolding molecule,S-SCAM)是由PDZ结构域、鸟苷酸激酶结构域和WW结构域组成的突触蛋白。它与N-甲基-D-天冬氨酸受体亚单位、神经连接素和β-连环蛋白相互作用。在这里,我们确定了Axin作为S-SCAM的新型结合伴侣。Axin与大鼠脑S-SCAM共免疫沉淀,在大鼠脑亚细胞分级中的突触后密度部分中检测到Axin,并且在神经元中与S-SCAM部分共定位。S-SCAM的鸟苷酸激酶结构域直接与Axin的GSK 3 β结合区结合。S-SCAM与β-连环蛋白和Axin形成复合物,但与GSK 3 β竞争Axin结合。因此,S-SCAM抑制了GSK 3 β对Axin介导的β-连环蛋白的磷酸化。
Synaptic scaffolding molecule (S-SCAM) is a synaptic protein that consists of PDZ domains, a guanylate kinase domain, and WW domains. It interacts with N-methyl-D-aspartate receptor subunits, neuroligin, and beta-catenin. Here, we identified Axin as a novel binding partner of S-SCAM. Axin was co-immunoprecipitated with S-SCAM from rat brain, detected in the post-synaptic density fraction in rat brain subcellular fractionation, and partially co-localized with S-SCAM in neurons. The guanylate kinase domain of S-SCAM directly bound to the GSK3beta-binding region of Axin. S-SCAM formed a complex with beta-catenin and Axin, but competed with GSK3beta for Axin-binding. Thereby, S-SCAM inhibited the Axin-mediated phosphorylation of beta-catenin by GSK3beta.