Related Experiment Video
Updated: Sep 27, 2025
12:52
Detection of Signaling Effector-Complexes Downstream of BMP4 Using in situ PLA, a Proximity Ligation Assay
Published on: March 3, 2011
31.9K
The context-dependent, combinatorial logic of BMP signaling
Heidi E Klumpe1, Matthew A Langley2, James M Linton2
1Division of Biology and Bioengineering, California Institute of Technology, Pasadena, CA 91125, USA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Cell Systems
|April 14, 2022
Summary
Bone morphogenetic protein (BMP) ligand combinations show context-dependent interactions. Receptor expression determines how BMP ligands synergize, revealing combinatorial logic in cell signaling.
Area of Science:
- Molecular Biology
- Cell Signaling
- Biochemistry
Background:
- Cell-cell communication relies on ligand-receptor interactions.
- Combinatorial signaling complexity arises from ligand and receptor variants.
- Understanding these interactions is crucial for developmental biology and therapeutics.
Purpose of the Study:
- To investigate the combinatorial logic of bone morphogenetic protein (BMP) ligand interactions.
- To determine how varying receptor expression affects BMP ligand synergy.
- To develop a model explaining context-dependent signaling outcomes.
Main Methods:
- Systematic measurement of pairwise BMP ligand interactions.
- Experiments conducted in cells with controlled receptor expression levels.
- Development and application of a biochemical model for signaling complex formation.
Main Results:
- BMP ligands were classified into equivalence groups based on synergistic interactions.
- Ligand synergy profiles varied significantly with receptor expression levels.
- A biochemical model accurately predicted context-dependent combinatorial interactions.
Conclusions:
- Receptor expression dictates the functional outcomes of BMP ligand combinations.
- This provides a framework for understanding combinatorial signaling in biological systems.
- Insights gained are applicable to developmental processes and therapeutic strategies involving BMPs.
Related Concept Videos
02:33Combinatorial Gene Control
8.5K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
8.5K
01:30Assembly of Signaling Complexes
6.0K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.0K
01:19Interactions Between Signaling Pathways
6.6K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.6K
01:22Diversity in Cell Signaling Responses
6.8K
The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity.
Graded and Abrupt Responses
Some signaling systems generate...
Graded and Abrupt Responses
Some signaling systems generate...
6.8K
01:24Intracellular Signaling Cascades
48.1K
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
48.1K
01:19Contact-dependent Signaling
45.2K
Contact-dependent signaling, as the name suggests, requires that communicating cells be in direct contact with each other. This is achieved either through receptor-ligand interactions or by specialized cytoplasmic channels that allow the flow of small molecules between cells. In animal cells, channels called gap junctions facilitate contact-dependent signaling in certain tissues, whereas, plasmodesmata perform a similar function in plants.
Gap Junctions
In animal cells, gap junctions are formed...
Gap Junctions
In animal cells, gap junctions are formed...
45.2K