LGI proteins in the nervous system.
LGI proteins in the nervous system.
复制标题
DOI：
10.1042/an20120095
复制
发表时间：
2013-06-25
期刊：
影响因子：
4.7
通讯作者：
Bermingham JR
中科院分区：
文献类型：
--
作者：
Kegel L;Aunin E;Meijer D;Bermingham JR
脊椎动物神经系统的发育和功能取决于不同细胞类型之间的特定相互作用。这种相互作用的两个例子是突触传递和髓鞘形成。LGI1-4(富含亮氨酸的胶质瘤灭活蛋白)在这些过程中发挥着重要作用。它们是由LRR(富含亮氨酸重复序列)结构域和所谓的癫痫相关或EPTP(表位蛋白)结构域组成的分泌性蛋白。这两个结构域都被认为在蛋白质之间的相互作用中起作用。第一个被鉴定的LGI基因，LGI1，在一个神经胶质瘤细胞系的染色体易位断裂点被发现。后来发现它在ADLTE(常染色体显性遗传性外侧颞叶癫痫)中发生突变，也被称为ADPEAF(常染色体显性遗传性部分性癫痫伴听力特征)。LGI1蛋白似乎作用于突触，抗LGI1的抗体可能导致自身免疫性疾病边缘脑炎。在犬良性家族性幼年癫痫中突变的LGI2在突触重构中也有类似的功能。LGI4是周围神经系统神经胶质细胞增殖所必需的，并与神经元受体ADAM22结合，促进雪旺细胞对轴突的包膜和髓鞘形成。因此，LGI蛋白在神经系统发育和功能中起着至关重要的作用，其研究对于了解其生物学功能和治疗潜力都是非常重要的。在这里，我们回顾了我们目前对这一重要蛋白质家族的了解，以及在了解其功能方面所取得的进展。
The development and function of the vertebrate nervous system depend on specific interactions between different cell types. Two examples of such interactions are synaptic transmission and myelination. LGI1-4 (leucine-rich glioma inactivated proteins) play important roles in these processes. They are secreted proteins consisting of an LRR (leucine-rich repeat) domain and a so-called epilepsy-associated or EPTP (epitempin) domain. Both domains are thought to function in protein–protein interactions. The first LGI gene to be identified, LGI1, was found at a chromosomal translocation breakpoint in a glioma cell line. It was subsequently found mutated in ADLTE (autosomal dominant lateral temporal (lobe) epilepsy) also referred to as ADPEAF (autosomal dominant partial epilepsy with auditory features). LGI1 protein appears to act at synapses and antibodies against LGI1 may cause the autoimmune disorder limbic encephalitis. A similar function in synaptic remodelling has been suggested for LGI2, which is mutated in canine Benign Familial Juvenile Epilepsy. LGI4 is required for proliferation of glia in the peripheral nervous system and binds to a neuronal receptor, ADAM22, to foster ensheathment and myelination of axons by Schwann cells. Thus, LGI proteins play crucial roles in nervous system development and function and their study is highly important, both to understand their biological functions and for their therapeutic potential. Here, we review our current knowledge about this important family of proteins, and the progress made towards understanding their functions.