Jiraiya attenuates BMP signaling by interfering with type II BMP receptors in neuroectodermal patterning.
During embryogenesis, bone morphogenetic protein (BMP) signaling needs to be finely tuned in a locally restricted manner. Here, we report a cell-intrinsic mode of BMP response control executed by the membrane protein Jiraiya. In the Xenopus embryo, zygotic Jiraiya, expressed exclusively in the neuroectoderm, is essential and sufficient for limiting dorsal neural development, which is dependent on BMP signals. In animal cap assays, Jiraiya selectively and cell-autonomously inhibits BMP signaling, while Jiraiya's knockdown enhances the signaling. In the cell, Jiraiya selectively forms a complex with type II BMP receptor (BMPRII) and downregulates the cell surface localization of functional BMPRII. This functional interaction with Jiraiya depends on the unique tail domain of BMPRII, and, in particular, the conserved EVNNNG motif, the function of which has been unknown. Thus, Jiraiya represents a cell-intrinsic cutoff mechanism for dynamic responsiveness to BMP signals via subtype-selective receptor control.
Aramaki
Toshihiro
T
Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
Sasai
Noriaki
N
Yakura
Rieko
R
Sasai
Yoshiki
Y
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000737:chemistry / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D017124:Conserved Sequence; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009420:Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D054258:Neural Plate / Q000196:embryology* / Q000378:metabolism; D009928:Organ Specificity; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015398:Signal Transduction / Q000235:genetics; D013329:Structure-Activity Relationship; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D008565:Membrane Proteins; C553322:TMEM221 protein, Xenopus; D029867:Xenopus Proteins; D052006:Bone Morphogenetic Protein Receptors, Type II