Spatial Restriction of Bone Morphogenetic Protein Signaling in Mouse Gastrula through the mVam2-Dependent Endocytic Pathway
Spatial Restriction of Bone Morphogenetic Protein Signaling in Mouse Gastrula through the mVam2-Dependent Endocytic Pathway
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DOI：
10.1016/j.devcel.2012.05.009
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发表时间：
2012-06-12
影响因子：
11.8
通讯作者：
Wada, Yoh
中科院分区：
文献类型：
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作者：
Aoyama, Minako;Sun-Wada, Ge-Hong;Wada, Yoh
胚胎体计划是通过各种信号级联的阳性和阴性控制建立的。晚期核内体和溶酶体被认为通过区室化信号分子来终止信号转导;然而，它们在胚胎发生中的作用仍然知之甚少。我们发现内吞途径通过调节信号传导活性参与发育过程。我们修改了小鼠Vam 2（mVam 2）基因座编码的调节膜贩运。mVam 2缺陷细胞表现出异常碎片化的晚期内体隔室。在去除TGF-β和EGF等生长因子后，突变细胞可以终止信号传导，但BMP-Smad 1/Smad 5信号传导除外。mVam 2缺陷的胚胎表现出异位激活BMP信号和胚胎图案的解体。我们发现，mVam 2，它与BMP I型受体相互作用，是需要的BMP信号的时空调制，通过螯合的受体复合物的后期阶段的内吞途径。
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-beta 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 spatio-temporal modulation of BMP signaling, via sequestration of the receptor complex in the late stages of the endocytic pathway.