A novel scaffold protein, TANC, possibly a rat homolog of Drosophila rolling pebbles (rols), forms a multiprotein complex with various postsynaptic density proteins
A novel scaffold protein, TANC, possibly a rat homolog of Drosophila rolling pebbles (rols), forms a multiprotein complex with various postsynaptic density proteins
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DOI：
10.1111/j.1460-9568.2005.03856.x
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发表时间：
2005-01-01
影响因子：
3.4
通讯作者：
Endo, S
中科院分区：
文献类型：
--
作者：
Suzuki, T;Li, WD;Endo, S
我们从大鼠大脑中克隆出一个新基因tanc（GenBank™登录号AB098072），该基因编码的蛋白质含有3个四肽重复序列（TPRs）、10个锚蛋白重复序列以及一个卷曲螺旋结构域，它可能是果蝇“滚动卵石”（rols）基因在大鼠中的同源基因。tanc基因在成年大鼠大脑中广泛表达。亚细胞定位、大脑免疫组织化学研究以及培养神经元细胞的免疫细胞化学研究表明，200kDa的TANC蛋白定位于突触后。蛋白质体外结合实验表明，TANC蛋白通过其C端的PDZ结合基序 -ESNV与PSD - 95、SAP97和Homer结合，通过其锚蛋白重复序列以及TPRs与卷曲螺旋结构域共同作用与血影蛋白结合。TANC还与Ca2+/钙调蛋白依赖性蛋白激酶II的α亚基结合。免疫沉淀研究表明，TANC与多种突触后蛋白相关联，包括鸟苷酸激酶相关蛋白（GKAP）、α - 中间丝蛋白、N - 甲基 - D - 天冬氨酸（NMDA）型谷氨酸受体2B以及AMPA型谷氨酸受体（GluR1）亚基。这些结果表明，TANC蛋白可能通过与多种突触后致密物质蛋白形成多蛋白复合物，从而作为一种突触后支架成分发挥作用。
We cloned from the rat brain a novel gene, tanc (GenBank(TM) Accession No. AB098072), which encoded a protein containing three tetratricopeptide repeats (TPRs), ten ankyrin repeats and a coiled-coil region, and is possibly a rat homolog of Drosophila rolling pebbles (rols). The tanc gene was expressed widely in the adult rat brain. Subcellular distribution, immunohistochemical study of the brain and immunocytochemical studies of cultured neuronal cells indicated the postsynaptic localization of TANC protein of 200 kDa. Pull-down experiments showed that TANC protein bound PSD-95, SAP97, and Homer via its C-terminal PDZ- binding motif, - ESNV, and fodrin via both its ankyrin repeats and the TPRs together with the coiled-coil domain. TANC also bound the a subunit of Ca2+/calmodulin-dependent protein kinase II. An immunoprecipitation study showed TANC association with various postsynaptic proteins, including guanylate kinase-associated protein ( GKAP), alpha-internexin, and N-methyl-D-aspartate ( NMDA)- type glutamate receptor 2B and AMPA-type glutamate receptor (GluR1) subunits. These results suggest that TANC protein may work as a postsynaptic scaffold component by forming a multiprotein complex with various postsynaptic density proteins.