LRRN6A/LERN1 (leucine-rich repeat neuronal protein 1), a novel gene with enriched expression in limbic system and neocortex
LRRN6A/LERN1 (leucine-rich repeat neuronal protein 1), a novel gene with enriched expression in limbic system and neocortex
复制标题
DOI：
10.1111/j.1460-9568.2003.03003.x
复制
发表时间：
2003-12-01
影响因子：
3.4
通讯作者：
Sumoy, L
中科院分区：
文献类型：
--
作者：
Carim-Todd, L;Escarceller, M;Sumoy, L
人染色体15 q24-q26是非常复杂的基因组区域，其含有几个片段性重复的区块，焦虑症的易感性已被定位到该区块（Gratacos等人，2001，Cell，106，367-379; Pujana等人，2001年，基因组研究，11，98-111）。通过对15 q24-q26区域的计算机基因含量分析，我们鉴定了一个新的基因LRRN 6A（leucine-rich repeat neuronal 6A），并证实了它位于这个复杂区域的着丝粒末端。LRRN 6A编码一种跨膜富含亮氨酸的重复蛋白，LERN 1（富含亮氨酸的重复神经元蛋白1），与参与轴突引导和迁移、神经系统发育和再生过程的蛋白质相似。在9号和19号染色体上与LRRN 6A同源的基因以及在小鼠基因组和其他生物体中的正向同源基因的鉴定表明，LERN蛋白构成了一个新的含LRR（富含亮氨酸重复序列）蛋白的亚家族。LRRN 6A表达模式对中枢神经系统是特异性的，在发育的早期阶段高度和广泛地表达，并且随着发育的进行逐渐限于前脑结构。成年期的表达水平一般较低，但在边缘系统和大脑皮层中保持稳定并显著富集。两者合计，LRRN 6A的表达谱的确认，其预测的蛋白质结构和其相似性的神经系统表达的LRR蛋白在神经系统发育和维护中的重要作用，表明LRRN 6A是一个新的基因的相关性在脊椎动物的分子和细胞神经生物学。
Human chromosome 15q24-q26 is a very complex genomic region containing several blocks of segmental duplications to which susceptibility to anxiety disorders has been mapped (Gratacos et al., 2001, Cell, 106, 367-379; Pujana et al., 2001, Genome Res., 11, 98-111). Through an in silico gene content analysis of the 15q24-q26 region we have identifie1d a novel gene, LRRN6A (leucine-rich repeat neuronal 6A), and confirmed its location to the centromeric end of this complex region. LRRN6A encodes a transmembrane leucine-rich repeat protein, LERN1 (leucine-rich repeat neuronal protein 1), with similarity to proteins involved in axonal guidance and migration, nervous system development and regeneration processes. The identification of homologous genes to LRRN6A on chromosomes 9 and 19 and the orthologous genes in the mouse genome and other organisms suggests that LERN proteins constitute a novel subfamily of LRR (leucine-rich repeat)-containing proteins. The LRRN6A expression pattern is specific to the central nervous system, highly and broadly expressed during early stages of development and gradually restricted to forebrain structures as development proceeds. Expression level in adulthood is lower in general but remains stable and significantly enriched in the limbic system and cerebral cortex. Taken together, the confirmation of LRRN6A's expression profile, its predicted protein structure and its similarity to nervous system-expressed LRR proteins with essential roles in nervous system development and maintenance suggest that LRRN6A is a novel gene of relevance in the molecular and cellular neurobiology of vertebrates.