Expression and localization of Cayman ataxia-related protein, Caytaxin, is regulated in a developmental- and spatial-dependent manner
Expression and localization of Cayman ataxia-related protein, Caytaxin, is regulated in a developmental- and spatial-dependent manner
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DOI：
10.1016/j.brainres.2006.10.068
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发表时间：
2007-01-19
期刊：
影响因子：
2.9
通讯作者：
Nakagawa, Toshiyuki
中科院分区：
文献类型：
--
作者：
Hayakawa, Yoshika;Itoh, Masanori;Nakagawa, Toshiyuki
编码Caytaxin的基因突变通过干扰正常剪接导致人类开曼共济失调，在突变的啮齿动物中，通过减少正常转录导致共济失调、肌张力障碍和智力迟钝。这些观察结果表明，Caytaxin可能对高级脑功能（如运动学习）至关重要。我们生成了针对小鼠Caytaxin的抗体。有趣的是，我们发现Caytaxin的表达在大脑发育过程中受到调控，而定量实时RT-PCR显示，在出生后7天（P7）至P14天，小脑和海马的mRNA水平没有变化，这表明Caytaxin的表达可能受到转录后机制的控制。免疫染色分析表明，Caytaxin定位于包括小脑和海马在内的许多脑区。此外，通过小鼠脑的亚细胞分离，Caytaxin被定位到突触前细胞质中，这一发现被与突触素I和VGLUT1共定位研究证实。上述数据、疾病表型和突变动物表明Caytaxin可能对突触功能至关重要。因此，确定Caytaxin在突触成熟中的作用可能会导致小脑共济失调和精神障碍的治疗干预措施的发展。(c) 2006 Elsevier B.V.版权所有
Mutation of the gene encoding Caytaxin causes human Cayman ataxia by interfering with normal splicing and, in mutant rodents, by reducing normal transcription, which leads to ataxia, dystonia, and mental retardation: These observations suggest that Caytaxin may be crucial for higher brain functions such as motor learning. We generated antibodies against mouse Caytaxin. Interestingly, we found that the expression of Caytaxin is regulated during brain development while quantitative real time RT-PCR indicated that the mRNA level did not change between postnatal days 7 (P7) and P14 in the cerebellum and hippocampus, implying that the expression of Caytaxin may be controlled by a post-transcriptional mechanism. Immunostaining analyses demonstrated that Caytaxin was localized in many brain areas including the cerebellum and hippocampus. Furthermore, Caytaxin was localized to the presynaptic cytosol by the subcellular fractionation of mouse brain and an observation that was confirmed by co-localization studies with synapsin I and VGLUT1. The above data, disease phenotypes, and mutant animals suggest that Caytaxin may be essential for synaptic function. Thus, identifying the role of Caytaxin in synapse maturation may lead to the development of therapeutic interventions for cerebellar ataxia as well as mental disorders. (c) 2006 Elsevier B.V. All rights reserved.