Tucker Richard P
Department of Cell Biology and Human Anatomy, University of California at Davis, Davis, CA, United States.
Front Neurosci. 2018 Dec 11;12:938. doi: 10.3389/fnins.2018.00938. eCollection 2018.
Disruption of teneurin expression results in abnormal neural networks, but just how teneurins support the development of the central nervous system remains an area of active research. This review summarizes some of what we know about the functions of the various domains of teneurins, the possible evolution of teneurins from a bacterial toxin, and the intriguing patterns of teneurin expression. Teneurins are a family of type-2 transmembrane proteins. The N-terminal intracellular domain can be processed and localized to the nucleus, but the significance of this nuclear localization is unknown. The extracellular domain of teneurins is largely composed of tyrosine-aspartic acid repeats that fold into a hollow barrel, and the C-terminal domains of teneurins are stuffed, and least partly, into the barrel. A 6-bladed beta-propeller is found at the other end of the barrel. The same arrangement-6-bladed beta-propeller, tyrosine-aspartic acid repeat barrel, and the C-terminal domain inside the barrel-is seen in toxic proteins from bacteria, and there is evidence that teneurins may have evolved from a gene encoding a prokaryotic toxin via horizontal gene transfer into an ancestral choanoflagellate. Patterns of teneurin expression are often, but not always, complementary. In the central nervous system, where teneurins are best studied, interconnected populations of neurons often express the same teneurin. For example, in the chicken embryo neurons forming the tectofugal pathway express teneurin-1, whereas neurons forming the thalamofugal pathway express teneurin-2. In , zebrafish and mice, misexpression or knocking out teneurin expression leads to abnormal connections in the neural networks that normally express the relevant teneurin. Teneurins are also expressed in non-neuronal tissue during development, and in at least some regions the patterns of non-neuronal expression are also complementary. The function of teneurins outside the nervous system remains unclear.
Ten-m蛋白表达的破坏会导致神经网络异常，但Ten-m蛋白如何支持中枢神经系统的发育仍是一个活跃的研究领域。本综述总结了我们对Ten-m蛋白各个结构域功能的一些了解、Ten-m蛋白可能从细菌毒素进化而来的情况以及Ten-m蛋白表达的有趣模式。Ten-m蛋白是一类2型跨膜蛋白。N端胞内结构域可被加工并定位于细胞核，但其核定位的意义尚不清楚。Ten-m蛋白的胞外结构域主要由酪氨酸-天冬氨酸重复序列组成，这些重复序列折叠成一个中空的桶状结构，Ten-m蛋白的C端结构域至少部分地填充在桶内。在桶的另一端发现了一个六叶β-螺旋桨结构。细菌的毒性蛋白中也存在同样的结构排列——六叶β-螺旋桨、酪氨酸-天冬氨酸重复序列桶以及桶内的C端结构域，并且有证据表明Ten-m蛋白可能是通过水平基因转移从一个编码原核毒素的基因进化而来，进入了祖先领鞭毛虫。Ten-m蛋白的表达模式通常（但并非总是）是互补的。在对Ten-m蛋白研究最为深入的中枢神经系统中，相互连接的神经元群体通常表达相同的Ten-m蛋白。例如，在鸡胚中，形成顶盖离中通路的神经元表达Ten-m1，而形成丘脑离中通路的神经元表达Ten-m2。在斑马鱼和小鼠中，Ten-m蛋白的错误表达或敲除会导致通常表达相关Ten-m蛋白的神经网络出现异常连接。在发育过程中，Ten-m蛋白也在非神经组织中表达，并在至少一些区域，非神经组织的表达模式也是互补的。Ten-m蛋白在神经系统之外的功能仍不清楚。
