Related Experiment Video
Updated: Jun 20, 2026
07:51
Pull-down of Calmodulin-binding Proteins
Published on: January 23, 2012
Neurogranin enhances synaptic strength through its interaction with calmodulin
Ling Zhong1, Tiffani Cherry, Christine E Bies
1Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226 0509, USA.
The EMBO Journal
|August 29, 2009
Summary
Neurogranin (Ng) enhances synaptic strength and mimics long-term potentiation (LTP) in the hippocampus. This protein
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Molecular Mechanisms
Background:
- Learning involves synaptic plasticity at CA1 hippocampal excitatory synapses.
- This plasticity depends on neuronal activity and NMDA receptor (NMDAR) activation.
- Molecular mechanisms linking plasticity stimuli to postsynaptic potentiation are not fully understood.
Purpose of the Study:
- Investigate the role of neurogranin (Ng) in synaptic plasticity.
- Elucidate the molecular mechanisms underlying Ng-mediated synaptic potentiation.
- Determine the necessity of Ng-calmodulin (CaM) interaction for potentiation.
Main Methods:
- Electrophysiological recordings of synaptic transmission.
- Manipulation of Ng expression and calmodulin binding.
- Knockdown of Ng to assess its role in LTP induction.
Main Results:
- Neurogranin (Ng) enhances postsynaptic sensitivity and synaptic strength in an activity- and NMDAR-dependent manner.
- Ng-mediated potentiation mimics and occludes long-term potentiation (LTP).
- Mutants of Ng unable to bind or dissociate from calmodulin (CaM) failed to potentiate synaptic transmission, indicating regulated Ng-CaM binding is crucial.
- Knocking down Ng blocked LTP induction.
Conclusions:
- Neurogranin (Ng) plays a critical role in postsynaptic potentiation at hippocampal CA1 synapses.
- Regulated Ng-calmodulin (CaM) interaction is essential for Ng-mediated synaptic strengthening.
- The Ng-CaM interaction provides a mechanistic link between the induction and expression of postsynaptic potentiation, crucial for learning and memory.
More Related Videos
Related Concept Videos
01:16Calmodulin-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,...
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
01:29Excitatory and Inhibitory Effects of Neurotransmitters
When an action potential reaches the presynaptic axon terminal, it releases neurotransmitters from the neuron into the synaptic cleft at a chemical synapse. The released neurotransmitter can be excitatory or inhibitory. The critical criteria commonly used to determine whether a molecule is a neurotransmitter at a chemical synapse are the molecule's presence in the presynaptic neuron. Second, its release is in response to strong presynaptic depolarization. And lastly, the presence of specific...
01:27Feedback 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...
01:26Neurochemical Transmission: Sites of Drug Action
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
01:20Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...