scholarly journals Scale invariance of BMP signaling gradients in zebrafish

2018 ◽  
Author(s):  
Yan Huang ◽  
David Umulis
Keyword(s):  
Scale Invariance ◽  
Bmp Signaling ◽  
Spatial Patterning ◽  
Protein Signaling ◽  
Wild Type ◽  
Bone Morphogenetic Protein Signaling ◽  
Cross Sectional ◽  
Morphogenetic Protein ◽  
Core Questions ◽  
Gradient Scaling

In both vertebrates and invertebrates, spatial patterning along the Dorsal-ventral (DV) embryonic axis depends on a morphogen gradient of Bone Morphogenetic Protein signaling. Scale invariance of DV patterning by BMPs has been found in both vertebrates and invertebrates, however the mechanisms that regulate gradient scaling remain controversial. To obtain quantitative data that can be used to address core questions of scaling, we introduce a method to tune the size of zebrafish embryos by reducing varying amounts of vegetal yolk. We quantified the BMP signaling gradient in wild-type and perturbed embryos and found that the system scales for reductions in cross-sectional perimeter of up to 30%. Furthermore, we found that the degree of scaling for intraspecies scaling within zebrafish is greater than that between Danioninae species.

scholarly journals A Survey of Strategies to Modulate the Bone Morphogenetic Protein Signaling Pathway: Current and Future Perspectives

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Jonathan W. Lowery ◽  
Brice Brookshire ◽  
Vicki Rosen
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Bmp Signaling ◽  
Protein Signaling ◽  
Bone Morphogenetic Protein Signaling ◽  
Human Organ ◽  
Morphogenetic Protein ◽  
Organ Systems ◽  
Bmp Pathway ◽  
Wide Perspective ◽  
The Relationship

Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the TGF-βfamily of ligands and are unequivocally involved in regulating stem cell behavior. Appropriate regulation of canonical BMP signaling is critical for the development and homeostasis of numerous human organ systems, as aberrations in the BMP pathway or its regulation are increasingly associated with diverse human pathologies. In this review, we provide a wide-perspective on strategies that increase or decrease BMP signaling. We briefly outline the current FDA-approved approaches, highlight emerging next-generation technologies, and postulate prospective avenues for future investigation. We also detail how activating other pathways may indirectly modulate BMP signaling, with a particular emphasis on the relationship between the BMP and Activin/TGF-βpathways.

scholarly journals Membrane targeting of inhibitory Smads through palmitoylation controls TGF-β/BMP signaling

2017 ◽  
Vol 114 (50) ◽  
pp. 13206-13211 ◽  
Author(s):  
Wenqing Li ◽  
Weini Li ◽  
Lihui Zou ◽  
Shanming Ji ◽  
Chaoyi Li ◽  
...  
Keyword(s):  
Cellular Membrane ◽  
Bmp Signaling ◽  
Tissue Homeostasis ◽  
Membrane Association ◽  
Type I ◽  
Protein Signaling ◽  
Bone Morphogenetic Protein Signaling ◽  
Stem Cell Regulation ◽  
Morphogenetic Protein ◽  
Signaling Activity

TGF-β/BMP (bone morphogenetic protein) signaling pathways play conserved roles in controlling embryonic development, tissue homeostasis, and stem cell regulation. Inhibitory Smads (I-Smads) have been shown to negatively regulate TGF-β/BMP signaling by primarily targeting the type I receptors for ubiquitination and turnover. However, little is known about how I-Smads access the membrane to execute their functions. Here we show that Dad, the Drosophila I-Smad, associates with the cellular membrane via palmitoylation, thereby targeting the BMP type I receptor for ubiquitination. By performing systematic biochemistry assays, we characterized the specific cysteine (Cys556) essential for Dad palmitoylation and membrane association. Moreover, we demonstrate that dHIP14, a Drosophila palmitoyl acyl-transferase, catalyzes Dad palmitoylation, thereby inhibiting efficient BMP signaling. Thus, our findings uncover a modification of the inhibitory Smads that controls TGF-β/BMP signaling activity.

scholarly journals Cooperative Inhibition of Bone Morphogenetic Protein Signaling by Smurf1 and Inhibitory Smads

2003 ◽  
Vol 14 (7) ◽  
pp. 2809-2817 ◽  
Author(s):  
Gyo Murakami ◽  
Tetsuro Watabe ◽  
Kunio Takaoka ◽  
Kohei Miyazono ◽  
Takeshi Imamura
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Mammalian Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Bmp Signaling ◽  
Type I ◽  
Protein Signaling ◽  
Reporter Construct ◽  
Bone Morphogenetic Protein Signaling ◽  
Morphogenetic Protein

Smad ubiquitin regulatory factor (Smurf) 1 binds to receptor-regulated Smads for bone morphogenetic proteins (BMPs) Smad1/5 and promotes their degradation. In addition, Smurf1 associates with transforming growth factor-β type I receptor through the inhibitory Smad (I-Smad) Smad7 and induces their degradation. Herein, we examined whether Smurf1 negatively regulates BMP signaling together with the I-Smads Smad6/7. Smurf1 and Smad6 cooperatively induced secondary axes in Xenopus embryos. Using a BMP-responsive promoter-reporter construct in mammalian cells, we found that Smurf1 cooperated with I-Smad in inhibiting BMP signaling and that the inhibitory activity of Smurf1 was not necessarily correlated with its ability to bind to Smad1/5 directly. Smurf1 bound to BMP type I receptors via I-Smads and induced ubiquitination and degradation of these receptors. Moreover, Smurf1 associated with Smad1/5 indirectly through I-Smads and induced their ubiquitination and degradation. Smurf1 thus controls BMP signaling with and without I-Smads through multiple mechanisms.

scholarly journals The Cdc42-selective GAP Rich regulates postsynaptic development and retrograde BMP transsynaptic signaling

2010 ◽  
Vol 191 (3) ◽  
pp. 661-675 ◽  
Author(s):  
Minyeop Nahm ◽  
A. Ashleigh Long ◽  
Sang Kyoo Paik ◽  
Sungdae Kim ◽  
Yong Chul Bae ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Molecular Mechanisms ◽  
Protein Signaling ◽  
Wild Type ◽  
Bone Morphogenetic Protein Signaling ◽  
Synaptic Growth ◽  
Morphogenetic Protein ◽  
Guanosine Triphosphatase ◽  
And Function ◽  
Syndrome Protein

Retrograde bone morphogenetic protein signaling mediated by the Glass bottom boat (Gbb) ligand modulates structural and functional synaptogenesis at the Drosophila melanogaster neuromuscular junction. However, the molecular mechanisms regulating postsynaptic Gbb release are poorly understood. In this study, we show that Drosophila Rich (dRich), a conserved Cdc42-selective guanosine triphosphatase–activating protein (GAP), inhibits the Cdc42–Wsp pathway to stimulate postsynaptic Gbb release. Loss of dRich causes synaptic undergrowth and strongly impairs neurotransmitter release. These presynaptic defects are rescued by targeted postsynaptic expression of wild-type dRich but not a GAP-deficient mutant. dRich inhibits the postsynaptic localization of the Cdc42 effector Wsp (Drosophila orthologue of mammalian Wiskott-Aldrich syndrome protein, WASp), and manifestation of synaptogenesis defects in drich mutants requires Wsp signaling. In addition, dRich regulates postsynaptic organization independently of Cdc42. Importantly, dRich increases Gbb release and elevates presynaptic phosphorylated Mad levels. We propose that dRich coordinates the Gbb-dependent modulation of synaptic growth and function with postsynaptic development.

scholarly journals Bone morphogenetic protein signaling in inflammation

2019 ◽  
Vol 244 (2) ◽  
pp. 147-156 ◽  
Author(s):  
David H Wu ◽  
Antonis K Hatzopoulos
Keyword(s):  
Bone Morphogenetic Protein ◽  
Bmp Signaling ◽  
Therapeutic Interventions ◽  
Protein Signaling ◽  
Bone Morphogenetic Protein Signaling ◽  
Morphogenetic Protein ◽  
Therapeutic Value ◽  
Organ Systems ◽  
Different Tissues

Bone morphogenetic protein signaling has long been established as a crucial pathway during embryonic development. In recent years, our knowledge of the function of bone morphogenetic protein signaling has expanded dramatically beyond solely its important role in development. Today, the pathway is known to have important homeostatic functions across multiple different tissues in the adult. Even more importantly, bone morphogenetic protein signaling is now known to function as a driver of diseases in the adult spanning different organ systems. In this review, we will explore the functions of bone morphogenetic protein signaling in diseases of inflammation. Through this exploration, we will highlight the value and challenges in targeting bone morphogenetic protein signaling for therapeutic interventions. Impact statement By compiling findings from recent studies, this review will garner novel insight on the dynamic and complex role of BMP signaling in diseases of inflammation, highlighting the specific roles played by both individual ligands and endogenous antagonists. Ultimately, this summary will help inform the high therapeutic value of targeting this pathway for modulating diseases of inflammation.

Sign in / Sign up

Export Citation Format

Share Document