Fung Wong Yan, Fat Ko Frankie Chi, Eng Cheah Kathryn Song, Lau Chow King
Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, PR China.
Dev Biol. 2007 Nov 1;311(1):95-105. doi: 10.1016/j.ydbio.2007.08.016. Epub 2007 Aug 16.
We have identified in Caenorhabditis elegans a homologue of the vertebrate Crim1, crm-1, which encodes a putative transmembrane protein with multiple cysteine-rich (CR) domains known to have bone morphogenetic proteins (BMPs) binding activity. Using the body morphology of C. elegans as an indicator, we showed that attenuation of crm-1 activity leads to a small body phenotype reminiscent of that of BMP pathway mutants. We showed that the crm-1 loss-of-function phenotype can be rescued by constitutive supply of sma-4 activity. crm-1 can enhance BMP signaling and this activity is dependent on the presence of the DBL-1 ligand and its receptors. crm-1 is expressed in neurons at the ventral nerve cord, where the DBL-1 ligand is produced. However, ectopic expression experiments reveal that crm-1 gene products act outside the DBL-1 producing cells and function non-autonomously to facilitate dbl/sma pathway signaling to control body size.
我们在秀丽隐杆线虫中鉴定出了脊椎动物Crim1的同源物crm-1，它编码一种推定的跨膜蛋白，该蛋白具有多个已知具有骨形态发生蛋白（BMP）结合活性的富含半胱氨酸（CR）的结构域。以秀丽隐杆线虫的身体形态为指标，我们发现crm-1活性的减弱会导致体型变小的表型，这与BMP信号通路突变体的表型相似。我们发现，通过组成型提供sma-4活性可以挽救crm-1功能丧失的表型。crm-1可以增强BMP信号传导，并且这种活性依赖于DBL-1配体及其受体的存在。crm-1在腹侧神经索的神经元中表达，而DBL-1配体正是在那里产生的。然而，异位表达实验表明，crm-1基因产物在产生DBL-1的细胞外起作用，并且通过非自主功能促进dbl/sma信号通路传导以控制体型。
