The various bone morphogenetic protein (BMP) signaling factors play an important role in early neural development in the vertebrate embryo. However, maturation of these tissues ultimately depends on the coordinated activity of factors that suppress BMP activity within the neuroectoderm, a cell population that ultimately gives rise to the nervous system.
Yoshiki Sasai and colleagues at the RIKEN Center for Developmental Biology in Kobe have now revealed a novel regulator of BMP signaling, Jiraiya1, which they originally identified in a screen for genes activated by the BMP inhibitor Chordin in the African clawed frog, Xenopus laevis2. “Jiraiya was intriguing as it encoded a novel membrane protein that had no homology to known proteins, and its expression was neural-specific,” says Sasai.
Unexpectedly, his team determined that the Jiraiya protein acts as a specific inhibitor of BMPRII, one of two core subunits of the BMP receptor, within the neuroectoderm (Fig. 1). BMPRII chemically modifies BMPRI in response to BMP binding; BMPRI subsequently activates downstream components of the signaling cascade. Initial experiments showed that Jiraiya specifically interferes with signaling at a point between ligand binding and BMPRI activation.
When overexpressed in cultured embryonic frog cells, Jiraiya depleted BMPRII from the plasma membrane by sequestering it within complexes in the cytoplasm. Evidence suggests that this protein physically interferes with the delivery of newly synthesized receptor molecules to the cell surface.
BMPRII is part of a larger family of receptor proteins that are relatively similar to one another, but features a distinctive ‘C-terminal tail domain’ (TD) that contains within it the specific Jiraiya-binding motif. This enigmatic ‘EVNNNG’ sequence appears to be a unique feature of BMPRII, although it is closely conserved in receptor homologues from other species. Transplantation of the motif onto a different receptor, ActRIIA, was sufficient to make that protein susceptible to similar Jiraiya-mediated inhibition. “The most intriguing part is that it acts only on the type II subunit of BMPR via this tail-domain whose role in dynamic signaling modulation had not been known,” says Sasai.
He and his colleagues conclude that Jiraiya appears to represent an important mechanism for the cell-specific inactivation of BMP-responsive pathways, and thereby helps define the boundaries of neural tissue development. The Jiraiya gene is found in a broad range of vertebrate species, although expression in the mouse embryo does not seem to follow the same neural-specific pattern of localization seen in frog embryos. Sasai hopes to further clarify its role in mammalian development in future studies.
The corresponding author for this highlight is based at the Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology
Journal informationAramaki, T., Sasai, N., Yakura, R. & Sasai, Y. Jiraiya attenuates BMP signaling by interfering with Type II BMP receptors in neuroectodermal patterning. Developmental Cell 19, 547–561 (2010).
Sasai, N., Mizuseki, K. & Sasai, Y. Requirement of FoxD3-class signaling for neural crest determination in Xenopus. Development 128, 2525–2536 (2001).
Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie
Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
21.04.2017 | Physics and Astronomy
21.04.2017 | Health and Medicine
21.04.2017 | Physics and Astronomy