ISM1 regulates NODAL signaling and asymmetric organ morphogenesis during development

We report that ISM1 is an inhibitor of NODAL signaling. ISM1 has little effect on TGF-β1, ACTIVIN-A, or BMP4 signaling but specifically inhibits NODAL-induced phosphorylation of SMAD2. In line with this observation, ectopic ISM1 causes defective left-right asymmetry and abnormal heart positioning in chick embryos. Mechanistically, ISM1 interacts with NODAL ligand and type I receptor ACVR1B through its AMOP domain, which compromises the NODAL–ACVR1B interaction and down-regulates phosphorylation of SMAD2. Therefore, we identify ISM1 as an extracellular antagonist of NODAL and reveal a negative regulatory mechanism that provides greater plasticity for the fine-tuning of NODAL signaling.

Source: Journal of Cell Biology - June 30, 2019 Category: Cytology Authors: Osorio, L., Wu, X., Wang, L., Jiang, Z., Neideck, C., Sheng, G., Zhou, Z. Tags: Adhesion, Cell Signaling, Biochemistry, Development Articles Source Type: research