Related Experiment Video
Updated: May 30, 2026

06:49
Automated Analysis of Dynamic Ca2+ Signals in Image Sequences
Published on: June 16, 2014
Parallel adaptive feedback enhances reliability of the Ca2+ signaling system
Ellen Abell1, Robert Ahrends, Samuel Bandara
1Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
Summary
Cells maintain accurate signaling despite protein variations by sensing calcium levels and adjusting key protein concentrations. This adaptive feedback system prevents signal transmission failure.
Area of Science:
- Cellular biology
- Biochemistry
- Systems biology
Background:
- Cells exhibit significant variations in signaling protein concentrations.
- Accurate signal transmission persists despite these variations, posing a challenge to understanding cellular regulation.
- The fundamental calcium signaling pathway is crucial for cellular function.
Purpose of the Study:
- To investigate how cells maintain accurate signaling despite protein concentration variability.
- To elucidate the regulatory mechanisms preventing signal transmission failure in calcium signaling.
- To understand the role of adaptive feedback in cellular signal processing.
Main Methods:
- Quantitative modeling to simulate cellular signaling dynamics.
- RNA interference (RNAi) to manipulate gene expression.
- Targeted selective reaction monitoring (SRM) mass spectrometry for precise protein quantification.
- Analysis of cytosolic and endoplasmic reticulum (ER) calcium (Ca2+) levels.
Main Results:
- Cells actively monitor cytosolic and ER Ca2+ concentrations.
- Cells concurrently adjust expression levels of STIM, PMCA, and SERCA in response to Ca2+ levels.
- Parallel regulation of these proteins effectively stabilizes basal Ca2+ levels.
- This regulatory strategy preserves essential receptor signaling functions.
Conclusions:
- Cells employ parallel adaptive feedback mechanisms, not just forward regulation, to ensure signal fidelity.
- Sensing pathway state and implementing multiple feedbacks are key to preventing transmission failure.
- This adaptive system maintains cellular signaling accuracy despite inherent molecular noise.
Related Concept Videos
Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Feedback Regulation of Calcium Concentration
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Cell Signaling Feedback Loops
Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
Amplifying Signals via Second Messengers
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
Intracellular Signaling Cascades
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...
Long-term Potentiation
Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
Hebbian LTP
LTP can occur when presynaptic neurons...
Hebbian LTP
LTP can occur when presynaptic neurons...

