title: Small C-terminal Domain Phosphatase 3 Dephosphorylates the Linker Sites of Receptor-regulated Smads (R-Smads) to Ensure Transforming Growth Factor β (TGFβ)-mediated Germ Layer Induction in Xenopus Embryos.
abstract: Germ layer induction is one of the earliest events shortly after fertilization that initiates body formation of vertebrate embryos. In Xenopus, the maternally deposited transcriptional factor VegT promotes the expression of zygotic Nodal/Activin ligands that further form a morphogen gradient along the vegetal-animal axis and trigger the induction of the three germ layers. Here we found that SCP3 (small C-terminal domain phosphatase 3) is maternally expressed and vegetally enriched in Xenopus embryos and is essential for the timely induction of germ layers. SCP3 is required for the full activation of Nodal/Activin and bone morphogenetic protein signals and functions via dephosphorylation in the linker regions of receptor-regulated Smads. Consistently, the linker regions of receptor-regulated Smads are heavily phosphorylated in fertilized eggs, and this phosphorylation is gradually removed when embryos approach the midblastula transition. Knockdown of maternal SCP3 attenuates these dephosphorylation events and the activation of Nodal/Activin and bone morphogenetic protein signals after midblastula transition. This study thus suggested that the maternal SCP3 serves as a vegetally enriched, intrinsic factor to ensure a prepared status of Smads for their activation by the upcoming ligands during germ layer induction of Xenopus embryos.
authors.affiliation: From the MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Guanni
authors.initials: G
authors.lastname: Sun
authors.affiliation: the Bioinformatics Division, Center for Synthetic and Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China.
authors.forename: Zhirui
authors.initials: Z
authors.lastname: Hu
authors.affiliation: the School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zheying
authors.initials: Z
authors.lastname: Min
authors.affiliation: the State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China, and.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yan
authors.affiliation: From the MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zhenpo
authors.initials: Z
authors.lastname: Guan
authors.affiliation: From the MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Hanxia
authors.initials: H
authors.lastname: Su
authors.affiliation: From the MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.affiliation: the Bioinformatics Division, Center for Synthetic and Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Ma
authors.affiliation: the State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China, and.
authors.forename: Ye-Guang
authors.initials: YG
authors.lastname: Chen
authors.affiliation: the Bioinformatics Division, Center for Synthetic and Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China, the Department of Biological Sciences, Center for Systems Biology, University of Texas at Dallas, Richardson, Texas 75080 michael.zhang@utdallas.edu.
authors.forename: Michael Q
authors.initials: MQ
authors.lastname: Zhang
authors.affiliation: the School of Life Sciences, Tsinghua University, Beijing 100084, China, qhtaolab@mail.tsinghua.edu.cn.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Tao
authors.affiliation: From the MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China, wwu@mail.tsinghua.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D028341:Activins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D036703:Blastula / Q000196:embryology / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D005260:Female; D005775:Gastrula / Q000196:embryology / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005855:Germ Layers / Q000196:embryology / Q000378:metabolism; D008024:Ligands; D055456:Nodal Signaling Ligands / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D051896:Smad Proteins, Receptor-Regulated / Q000737:chemistry / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D008024:Ligands; D055456:Nodal Signaling Ligands; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051896:Smad Proteins, Receptor-Regulated; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D028341:Activins; D010749:Phosphoprotein Phosphatases
keywords: SCP3; SMAD transcription factor; Xenopus; embryo; germ layer induction; phosphatase; transforming growth factor beta (TGF-beta)