Transglutaminase 6: a protein associated with central nervous system development and motor function.
Transglutaminase 6: a protein associated with central nervous system development and motor function.
复制标题
DOI：
10.1007/s00726-011-1091-z
复制
发表时间：
2013-01
期刊：
影响因子：
3.5
通讯作者：
Aeschlimann, Daniel
中科院分区：
文献类型：
--
作者：
Thomas, Helen;Beck, Konrad;Adamczyk, Magdalena;Aeschlimann, Pascale;Langley, Martin;Oita, Radu C.;Thiebach, Lars;Hils, Martin;Aeschlimann, Daniel
转谷氨酰胺酶（TG）形成催化蛋白质和肽中谷氨酰胺残基的各种翻译后修饰的酶家族，包括分子内和分子间异肽键形成、酯化和脱酰胺。我们已经确定了哺乳动物TG家族的一个新成员，TG 6，它在具有神经元特征的人癌细胞系和小鼠脑中表达。除了全长蛋白质外，选择性剪接导致人中缺少第二个β-桶结构域的短变体和小鼠中具有截短的β-夹心结构域的变体。生化数据表明，TG 6是由钙离子和鸟嘌呤核苷酸变构调节。分子模拟表明，TG 6可能有Ca 2+和GDP结合位点相关的TG 3和TG 2，分别。在小鼠中的mRNA和蛋白质的定位鉴定了TG 6在中枢神经系统中的丰富表达。其在小鼠发育中诱导的时间和空间模式的分析表明与神经发生相关。TG 6的神经元表达通过用细胞类型特异性标记物双标记小鼠前脑细胞来证实。用NGF或二丁酰cAMP诱导小鼠Neuro 2a细胞分化与TG 6表达上调相关。家族性共济失调最近被认为与TGM 6基因突变有关。在谷蛋白敏感性患者的免疫介导的共济失调中发现了TG 6自身抗体。这些发现表明TG 6在皮质和小脑神经元中起关键作用。本文的在线版本（doi：10.1007/s 00726 -011-1091-z）包含补充材料，可供授权用户使用。
Transglutaminases (TG) form a family of enzymes that catalyse various post-translational modifications of glutamine residues in proteins and peptides including intra- and intermolecular isopeptide bond formation, esterification and deamidation. We have characterized a novel member of the mammalian TG family, TG6, which is expressed in a human carcinoma cell line with neuronal characteristics and in mouse brain. Besides full-length protein, alternative splicing results in a short variant lacking the second β-barrel domain in man and a variant with truncated β-sandwich domain in mouse. Biochemical data show that TG6 is allosterically regulated by Ca2+ and guanine nucleotides. Molecular modelling indicates that TG6 could have Ca2+ and GDP-binding sites related to those of TG3 and TG2, respectively. Localization of mRNA and protein in the mouse identified abundant expression of TG6 in the central nervous system. Analysis of its temporal and spatial pattern of induction in mouse development indicates an association with neurogenesis. Neuronal expression of TG6 was confirmed by double-labelling of mouse forebrain cells with cell type-specific markers. Induction of differentiation in mouse Neuro 2a cells with NGF or dibutyryl cAMP is associated with an upregulation of TG6 expression. Familial ataxia has recently been linked to mutations in the TGM6 gene. Autoantibodies to TG6 were identified in immune-mediated ataxia in patients with gluten sensitivity. These findings suggest a critical role for TG6 in cortical and cerebellar neurons. The online version of this article (doi:10.1007/s00726-011-1091-z) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
3.7
作者：
Boscolo S;Lorenzon A;Sblattero D;Florian F;Stebel M;Marzari R;Not T;Aeschlimann D;Ventura A;Hadjivassiliou M;Tongiorgi E
通讯作者：
Tongiorgi E
影响因子：
4.1
作者：
Candi, E;Paradisi, A;Melino, G
通讯作者：
Melino, G
影响因子：
12.8
作者：
Ahvazi, B;Steinert, PM
通讯作者：
Steinert, PM
影响因子：
4.8
作者：
CANDI, E;MELINO, G;STEINERT, PM
通讯作者：
STEINERT, PM
影响因子：
11.4
作者：
Ahvazi, B;Kim, HC;Steinert, PM
通讯作者：
Steinert, PM