Division of Biological Science, Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
Dev Cell. 2012 Jun 12;22(6):1163-75. doi: 10.1016/j.devcel.2012.05.009.
The embryonic body plan is established through positive and negative control of various signaling cascades. Late endosomes and lysosomes are thought to terminate signal transduction by compartmentalizing the signaling molecules; however, their roles in embryogenesis remain poorly understood. We showed here that the endocytic pathway participates in the developmental program by regulating the signaling activity. We modified the mouse Vam2 (mVam2) locus encoding a regulator of membrane trafficking. mVam2-deficient cells exhibited abnormally fragmented late endosomal compartments. The mutant cells could terminate signaling after the removal of the growth factors including TGF-β and EGF, except BMP-Smad1/Smad5 signaling. mVam2-deficient embryos exhibited ectopic activation of BMP signaling and disorganization of embryo patterning. We found that mVam2, which interacts with BMP type I receptor, is required for the spatiotemporal modulation of BMP signaling, via sequestration of the receptor complex in the late stages of the endocytic pathway.
胚胎体模式是通过各种信号级联的正、负调控建立的。晚期内体和溶酶体通过分隔信号分子来终止信号转导，但其在胚胎发生中的作用仍知之甚少。我们在这里表明，内吞途径通过调节信号活性参与发育程序。我们修饰了编码膜运输调节剂的小鼠 Vam2 (mVam2) 基因座。mVam2 缺陷细胞表现出晚期内体区室异常碎片化。突变细胞在去除 TGF-β 和 EGF 等生长因子后可以终止信号转导，除了 BMP-Smad1/Smad5 信号转导。mVam2 缺陷胚胎表现出 BMP 信号的异位激活和胚胎模式的紊乱。我们发现，与 BMP Ⅰ型受体相互作用的 mVam2 通过在晚期内吞途径中将受体复合物隔离，用于 BMP 信号的时空调节。
