Related Experiment Video
Updated: Apr 22, 2026
07:51
Pull-down of Calmodulin-binding Proteins
Published on: January 23, 2012
24.2K
Mission CaMKIIγ: shuttle calmodulin from membrane to nucleus
Zulfiqar A Malik1, Ivar S Stein1, Manuel F Navedo1
1Department of Pharmacology, University of California, Davis, Davis, CA 95615, USA.
Cell
|October 11, 2014
Summary
Calcium influx into neurons triggers gene transcription. The study reveals that CaMKIIγ acts as a carrier, transporting activated Calmodulin (CaM) from cell surface calcium channels to the nucleus, explaining a key step in neuronal plasticity.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Neuronal plasticity, essential for learning and memory, is regulated by calcium (Ca2+) influx.
- Activity-dependent gene transcription in neurons is initiated by Ca2+-activated Calmodulin (CaM).
- The mechanism by which Ca2+-bound CaM translocates to the nucleus from the cell membrane remained unclear.
Purpose of the Study:
- To elucidate the transport mechanism of Calmodulin (CaM) from the plasma membrane to the nucleus in neurons.
- To identify the molecular players involved in CaM nuclear translocation following calcium influx.
- To understand the role of CaMKIIγ in mediating CaM's journey to the nucleus.
Main Methods:
- Utilized advanced imaging techniques to track CaM localization in response to calcium signaling.
- Employed biochemical assays to investigate protein-protein interactions between CaM and CaMKIIγ.
- Performed genetic manipulation studies to assess the necessity of CaMKIIγ for CaM nuclear transport.
Main Results:
- Demonstrated that CaMKIIγ directly binds to Calmodulin (CaM) upon calcium influx.
- Showed that CaMKIIγ facilitates the movement of CaM from cell surface Ca2+ channels towards the nucleus.
- Confirmed that CaMKIIγ is essential for the nuclear accumulation of CaM and subsequent gene transcription.
Conclusions:
- CaMKIIγ serves as a crucial shuttle protein, transporting activated Calmodulin (CaM) to the nucleus.
- This CaMKIIγ-mediated transport pathway is a key mechanism linking cell surface calcium signaling to nuclear events driving neuronal plasticity.
- The findings provide novel insights into the regulation of gene expression underlying neuronal function and adaptation.
More Related Videos
10:03Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins
Published on: August 10, 2014
11.4K
09:07Fluorescent Calcium Imaging and Subsequent In Situ Hybridization for Neuronal Precursor Characterization in Xenopus laevis
Published on: February 18, 2020
9.4K
Related Concept Videos
01:16Calmodulin-dependent Signaling
4.8K
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,...
4.8K
01:15Amplifying Signals via Second Messengers
6.0K
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...
6.0K
01:07MAPK Signaling Cascades
7.2K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.2K
01:24Intracellular Signaling Cascades
44.6K
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...
44.6K
01:45Regulation of Nuclear Protein Sorting
2.5K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.5K
01:25cAMP-dependent Protein Kinase Pathways
7.2K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
7.2K