Department of Biochemistry and Molecular Biology, University of Melbourne, 3010 Victoria, Australia.
J Biol Chem. 2011 Jun 24;286(25):22546-57. doi: 10.1074/jbc.M110.217703. Epub 2011 Apr 19.
Predatory marine cone snails (genus Conus) utilize complex venoms mainly composed of small peptide toxins that target voltage- and ligand-gated ion channels in their prey. Although the venoms of a number of cone snail species have been intensively profiled and functionally characterized, nothing is known about the initiation of venom expression at an early developmental stage. Here, we report on the expression of venom mRNA in embryos of Conus victoriae and the identification of novel α- and O-conotoxin sequences. Embryonic toxin mRNA expression is initiated well before differentiation of the venom gland, the organ of venom biosynthesis. Structural and functional studies revealed that the embryonic α-conotoxins exhibit the same basic three-dimensional structure as the most abundant adult toxin but significantly differ in their neurological targets. Based on these findings, we postulate that the venom repertoire of cone snails undergoes ontogenetic changes most likely reflecting differences in the biotic interactions of these animals with their prey, predators, or competitors. To our knowledge, this is the first study to show toxin mRNA transcripts in embryos, a finding that extends our understanding of the early onset of venom expression in animals and may suggest alternative functions of peptide toxins during development.
掠食性海洋圆锥蜗牛(属 Conus)利用主要由靶向其猎物电压门控和配体门控离子通道的小肽毒素组成的复杂毒液。尽管已经对许多圆锥蜗牛物种的毒液进行了深入的剖析和功能表征,但对于在早期发育阶段开始表达毒液的情况却一无所知。在这里,我们报告了 Conus victoriae 胚胎中毒液 mRNA 的表达情况,并鉴定了新的α-和 O-芋螺毒素序列。胚胎毒素 mRNA 的表达早在毒液腺(毒液生物合成的器官)分化之前就开始了。结构和功能研究表明,胚胎α-芋螺毒素表现出与最丰富的成年毒素相同的基本三维结构,但在其神经靶标上有显著差异。基于这些发现,我们假设圆锥蜗牛的毒液库经历了个体发生变化,这很可能反映了这些动物与猎物、捕食者或竞争者之间生物相互作用的差异。据我们所知,这是第一项在胚胎中显示毒素 mRNA 转录本的研究,这一发现扩展了我们对动物毒液表达早期开始的理解,并且可能提示肽毒素在发育过程中具有替代功能。