Structural, gene expression, and functional analysis of the fugu (Takifugu rubripes) insulin-like growth factor binding protein-4 gene
Structural, gene expression, and functional analysis of the fugu (Takifugu rubripes) insulin-like growth factor binding protein-4 gene
复制标题
河豚 (Takifugu rubripes) 胰岛素样生长因子结合蛋白 4 基因的结构、基因表达和功能分析。
DOI：
10.1152/ajpregu.90439.2008
复制
发表时间：
2009-03-01
影响因子：
2.8
通讯作者：
Duan, Cunming
中科院分区：
文献类型：
--
作者：
Li, Mingyu;Li, Yun;Duan, Cunming
胰岛素样生长因子（IGF）信号通路是一条保守的调节动物发育、生长、代谢、生殖和衰老的通路。IGFs的生物学作用受IGF-binding proteins（IGFBPs）调节。虽然鱼类IGFBP-1、IGFBP-2、IGFBP-3和IGFBP-5的结构和功能已被阐明，但目前还没有关于鱼类IGFBP-4的全长结构及其生物学作用的报道。本研究克隆了河豚鱼IGFBP-4基因并进行了序列分析。序列比较、系统发育和同线性分析表明，其染色体位置、基因和蛋白质结构与哺乳动物同源物相似。河豚鱼IGFBP-4 mRNA在除脾脏外的所有成体组织中均可检测到。与年轻动物相比，老年动物的肌肉和眼睛中IGFBP-4 mRNA水平更高。饥饿导致肌肉、肝脏、胆囊和大脑中IGFBP-4 mRNA丰度显著增加。在斑马鱼胚胎中过量表达河豚和人IGFBP-4导致身体大小和体节数量显著减少，表明河豚IGFBP-4抑制生长和发育，可能是通过与IGF结合并抑制其与IGF受体的结合。这些结果提供了新的信息的结构和功能的保护，表达模式，以及在硬骨鱼IGFBP-4基因的生理调控。
The insulin-like growth factor (IGF) signaling pathway is a conserved pathway that regulates animal development, growth, metabolism, reproduction, and aging. The biological actions of IGFs are modulated by IGF-binding proteins (IGFBPs). Although the structure and function of fish IGFBP-1, -2, -3, and -5 have been elucidated, there is currently no report on the full-length structure of a fish IGFBP-4 nor its biological action. In this study, we cloned and characterized the IGFBP-4 gene from fugu. Sequence comparison, phylogenetic, and synteny analyses indicate that its chromosomal location, gene, and protein structure are similar to its mammalian orthologs. Fugu IGFBP-4 mRNA was easily detectable in all adult tissues examined with the exception of spleen. Older animals tended to have higher levels of IGFBP-4 mRNA in the muscle and eyes compared with younger animals. Starvation resulted in significant increases in IGFBP-4 mRNA abundance in the muscle, liver, gallbladder, and brain. Overexpression of fugu and human IGFBP-4 in zebrafish embryos caused a significant decrease in body size and somite number, suggesting that fugu IGFBP-4 inhibits growth and development, possibly by binding to IGFs and inhibiting their binding to the IGF receptors. These results provide new information about the structural and functional conservation, expression patterns, and physiological regulation of the IGFBP-4 gene in a teleost fish.